This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

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 effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged ≥50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.

Objective:To explore the clinical efficacy of operative treatment of geriatric pelvic fractures.Methods:A retrospective study was conducted to analyze the clinical data of 55 geriatric patients with pelvic fracture who had been operatively treated at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from January 2020 to October 2023. There were 13 males and 42 females with an age of 72.0 (68.0, 83.3) years. By the AO/OTA classification, there were 47 cases of type B and 8 cases of type C; by the classification for fragility fractures of pelvis, there were 5 cases of type Ⅱ, 44 cases of type Ⅲ, and 6 cases of type Ⅳ. The patients received operative treatment 4.0 (3.0, 6.3) days after injury. Of the 10 patients treated by open reduction and closed reduction, the posterior ring was fixated by a plate in 7 and by screws in 3, and the anterior ring was fixated by either a plate, an external fixator or a minimally invasive anterior pelvic ring internal fixator except in the 2 cases receiving no fixation. Of the other 45 patients treated by closed reduction and fixation, the posterior ring was all fixated by screws except in the 2 cases receiving no fixation, and the anterior ring was fixated by either screws, an external fixator or a minimally invasive anterior pelvic ring internal fixator except in the 10 cases receiving no fixation. The major peri-operative complications, quality of fracture reduction, mortality, and functional recovery of the pelvis at the last follow-up were recorded.Results:There were no major peri-operative complications. According to the Matta criteria, the quality of fracture reduction was excellent in 31, good in 14, fair in 8 and poor in 2 cases, giving a good to excellent rate of 81.8% (45/55). Fifty-four cases were followed up for (15.4±9.1) months and 1 case was lost to the follow-up. Four cases died within 1 year after operation, giving a mortality of 7.4% (4/54). The modified Majeed score at the last follow-up was 69 (54, 76) for the 46 cases who had been followed up for longer than 4 months; the functional recovery of the pelvis at the last follow-up was rated as excellent in 27 cases, as good in 8 cases and as fair in 11 cases, giving a good to excellent rate of 76.1% (35/46) according to the criteria proposed by the faculty of the writers. The internal fixation failed in 3 cases during the follow-up.Conclusion:For the geriatric pelvic fractures, operative treatment can lead to satisfactory clinical outcomes.

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 explore the feasibility and consistency of a new digital classification system of pelvic fractures named as JST classification based on close reduction techniques.Methods:A retrospective collection was conducted of the data from the 63 patients with pelvic fracture who had undergone surgical treatment after JST classification at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from March 2021 to March 2023. Digital classification of the pelvic fractures was performed based on their locations and displacements. The classification first divides the pelvis into 4 parts: left half pelvis and right half pelvis; sacral Denis Ⅲ area and pubic symphysis. The symmetrical left and right sacral Denis Ⅰ and Denis Ⅱ areas are also included in the left/right half pelvis. Subsequently, the left half pelvis and right half pelvis are divided into 4 regions and marked by capitalized English letters: Sacrum Area (including Denis Ⅰ and Denis Ⅱ, denoted as S), Sacroiliac Joint Area (denoted as J), Iliac Area (denoted as I), and Pubic Area (denoted as P); to distinguish right/left, R and L are used as prefixes. The 2 asymmetric parts are also marked with English letters: Denis Ⅲ area of the sacrum (denoted as Sac), and pubic symphysis (denoted as C). Afterwards, the fracture line morphology and displacement in each region are marked digitally to form a complete JST classification system. The inter- and intra-observer reliabilities (Fleiss' and Cohen's Kappa) of the JST classification system were tested by 3 observers with more than 10 years of experience in pelvic fracture treatment.Results:Consistency analysis of the JST classification results showed that the mean κ value of the intra-observer reliability was 0.818 (from 0.658 to 0.946, P<0.001) and the inter-observer reliability 0.873 (from 0.674 to 1.000, P<0.001), both indicating excellent agreement. Of the 63 patients, 59 obtained successful closed reduction with the assistance of the Rossum Robot R-Universal intelligent orthopedic surgical robot system after fracture classification by the JST system, yielding a success rate of 93.7% (59/63). Conclusions:The new JST classification system for pelvic fractures demonstrates strong intra and inter-observer reliabilities compared with traditional classification systems. As JST classification system labels each fracture site and key bones, it is of great significance for the deep learning and intraoperative operations of intelligent fracture robots.

Humans ; Aged ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal/adverse effects* ; Osteonecrosis/surgery* ; Femur Head Necrosis/surgery*

Objective:To compare the long-term clinical outcomes between cannulated screw internal fixation for stable femoral neck fractures and arthroplasty for unstable ones in the elderly patients.Methods:A retrospective study was conducted to analyze the 542 patients with femoral neck fracture who had been admitted to Department of Orthopedics and Traumatology, Beijing Jishuitan Hospital, Capital Medical University from May 2015 to April 2017. The 542 patients were divided into 2 groups based on fracture stability and treatment method. In the stable group (Garden type Ⅰ, type Ⅱ, and abduction compression type) of 121 cases who underwent cannulated screw internal fixation, there were 28 males and 93 females with a mean age of (77.6±8.1) years, and 20 cases of type Ⅰ, 101 cases of type Ⅱ, and 34 cases of abduction compression type by the Garden classification. In the unstable group (Garden type Ⅲ, type Ⅳ, and type Ⅱ with a posterior tilt angle >20°) of 421 cases who underwent arthroplasty, there were 130 males and 291 females with a mean age of (78.7 ± 6.9) years, and 14 cases of type Ⅱ, 403 cases of type Ⅲ, and 4 cases of type Ⅳ by the Garden classification. The postoperative mortality, reoperation rate, and mobility at the last follow-up were compared between the 2 groups.Results:There were no statistically significant differences in the baseline characteristics, except for serum albumin concentration and peripheral white blood cell count at admission, between the 2 groups, indicating comparability ( P>0.05). The hospital stay in the stable group [5.0 (4.0, 6.0)d] was significantly shorter than that in the unstable group [6.0 (5.0, 8.0)d], and the follow-up time for the stable group [54.4 (49.3, 58.7) months] significantly longer than that for the unstable group [52.2 (46.0, 59.3) months] ( P<0.05). A total of 158 patients (45 cases in the stable group and 113 cases in the unstable group) were lost to the last follow-up. At the last follow-up, the mortality in the stable group (18.4%, 14/76) was significantly lower than that in the unstable group (31.5%, 97/308), the reoperation rate in the former (15.8%, 12/76) significantly higher than that in the latter (3.6%, 11/308), and the capability of daily activities in the former (by the fracture mobility scoring: level 1 in 35 cases, level 2 in 13 cases, level 3 in 3 cases, level 4 in 2 cases, and level 5 in 1 case) significantly better than that in the latter (level 1 in 99 cases, level 2 in 47 cases, level 3 in 24 cases, level 4 in 22 cases, and level 5 in 5 cases) (all P<0.05). Conclusion:Compared with the arthroplasty for unstable femoral neck fractures, cannulated screw internal fixation for stable femoral neck fractures leads to a lower long-term mortality and a better capability of daily activities, but a significantly higher reoperation rate.

Objective:To elucidate the recent therapeutic efficacy of the intelligent fracture reduction robotic system in managing pelvic fractures.Methods:A retrospective evaluation of 49 pelvic fracture patients treated using the intelligent fracture reduction robotic system at Beijing Jishuitan Hospital's trauma orthopedics department between March 2021 and December 2022 was conducted. The cohort included 30 males and 19 females, with a mean age of 51.51±18.71 years (20-92 years range). Fractures were classified according to the Tile system: B1 type in 2 cases, B2 in 7, B3 in 3, C1 in 30, and C2 in 3. The median interval between injury and surgery was 6 days, with a range of 2-22 days. The robotic system assisted in pelvic fracture reduction and stabilization surgeries. Preoperative and postoperative evaluations involved pelvic CT scans, anteroposterior, inlet, and outlet radiographic images. Fracture displacement and reduction outcomes were assessed via X-ray imagery. Data captured included intraoperative blood loss, duration of surgery, fracture stabilization techniques, and postoperative monitoring period. The Majeed scoring system gauged functional outcomes.Results:Of the patients, 48 underwent minimally invasive interventions with robotic assistance, while one case necessitated open reduction and internal fixation due to an unsuccessful reduction. The duration between injury and operation ranged from 2 to 22 days. Average surgical time stood at 206.5±7.1 minutes (105-440 min range), and median intraoperative blood loss was 100ml (10-600 ml range). Using the Matta reduction criteria, 30 postoperative cases exhibited excellent and 9 good outcomes for posterior pelvic ring displacement, translating to a 93% (38/41) positive rate. For anterior pelvic ring shifts, 45 showed excellent and 3 good outcomes, culminating in a 100% (48/48) success rate. Follow-up for the 48 cases lasted 11.0 months (3-23 months range), with the Majeed functional score averaging 81.9±17.0 points (42-100 point range). 27 cases scored excellent, and 11 good, yielding a combined positive outcome rate of 79.2% (38/48).Conclusion:Employing the intelligent fracture reduction robotic system in pelvic fracture treatments facilitates minimally invasive interventions and yields favorable short-term clinical results.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.