BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

Objective:To analyze the factors influencing the ADL ability and the improvement degree of ADL ability at discharge of hospitalized patients with TBI and to establish prediction models. Method:Data of 220 patients with traumatic brain injury hospitalized in the department of neurorehabilitation,Beijing Boai hospital from september 2017 to september 2020 were retrospectively collected.They were ran-domly divided into training set and validation set according to 3:1,and descriptive analysis was conducted for all variables.BI score at discharge and BI score difference between admission and discharge were used as out-come indexes.Firstly,univariate analysis was used to screen the statistically significant influencing factors,and then multivariate logistic regression analysis was used to establish the prediction model.Receiver operating characteristic(ROC)curve,calibration curve and Hosmer-Lemeshow test were used to evaluate the differentia-tion and calibration of the model in the training set and validation set. Result:Two prediction models were established by multivariate logistic regression:①Duration of disease at ad-mission,FMB at admission and BI at admission were significant influencing factors of BI at discharge.The ar-ea under the curves of the prediction model with BI at discharge was 0.957(95％CI:0.930-0.983)and 0.917(95％CI:0.839-0.994)in the training set and validation set,respectively,showing good model differentiation.Hosmer-lemeshow test results were P=0.196 and P=0.551,respectively,indicating a good calibration degree of the model.The sensitivity,specificity,and Youden index of the logistic regression model were 91.4％(95％CI:0.833-0.959)、83.3％(95％CI:0.723-0.907)and 0.747,respectively.②The duration of disease,length of stay and age at admission significantly affected the BI difference.The areas of the established prediction mod-el under the curves of training set and validation set were 0.773(95％CI:0.702-0.844)and 0.747(95％CI:0.613-0.881),and Hosmer-Lemeshow test results were P=0.721 and P=0.274,respectively,indicating good model differentiation and calibration.The sensitivity,specificity,and Youden index of the logistic regression model were 77.2％(95％CI:0.670-0.850)、64.4％(95％CI:0.522-0.750)and 0.416,respectively. Conclusion:The established two prediction models will help rehabilitation doctors to preliminarily judge the level of functional independence at discharge and the degree of functional improvement during hospitalization according to the status of patients with TBI at admission,and provide reference for rehabilitation medical work.

Objective:To identify the risk factors, and develop and validate a risk prediction model for abnormal bone mass in end-stage renal disease (ESRD) patients.Methods:It was a retrospective cross-sectional study. The clinical and laboratory data of ESRD patients who were hospitalized in the Department of Nephrology, Zhongda Hospital Affiliated to Southeast University from January 2022 to May 2023 were collected retrospectively. The patients were randomly divided into training and validation cohorts at a ratio of 7∶3. They were further divided into normal and abnormal bone mass groups according to the T value measured by dual-energy X-ray absorptiometry (DXA). Then, backward stepwise regression and least absolute shrinkage and selection operator (LASSO) were respectively used to develop the risk prediction model for abnormal bone mass in ESRD patients. Akaike information criterion (AIC), bayesian information criterion (BIC), and accuracy were used to evaluate the performance of these two models, after which the preferable model was selected. Moreover, the receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test, and decision curve analyses (DCA) were applied to evaluate the diagnostic performance of the preferable model. Finally, a dynamic nomogram for individual assessment was constructed based on the preferable model.Results:A total of 254 ESRD patients were enrolled, including 160 (63.0%) males, 161 (63.4%) hemodialysis patients, and 202 (79.5%) patients with abnormal bone mass. There was no significant difference in the prevalence of abnormal bone mass between training group ( n=178) and validation group ( n=76) (79.2% vs. 80.3%, χ2=0.036, P=0.849). The final variables and variable parameters included in the LASSO and stepwise regression models were the same, which were five variables: age, body mass index, hypertension, diabetes, and osteocalcin. Both models also had the same AIC, BIC, and accuracy in the training group, which were 113.45, 132.54, and 0.837, respectively. Therefore, the LASSO model and the stepwise regression model performed consistently in this study and could be considered as the same model, hereafter referred to as the Model. The Model's area under the ROC curve in the training and validation groups was 0.923 (95% CI 0.884-0.963) and 0.809 (95% CI 0.675-0.943), respectively. The optimal cutoff for the training group was 0.858, with a sensitivity of 0.801, a specificity of 0.973 and an accuracy of 0.837; when this cutoff value was taken, the validation group's sensitivity was 0.689, specificity was 0.800, and accuracy was 0.711. The Model demonstrated excellent performance in the calibration curve, Hosmer-Lemeshow test ( P>0.05), and DCA. Finally, based on the five predictors of the Model, a dynamic nomogram was created for clinicians to enter baseline clinical parameters for early identification of high-risk patients with abnormal bone mass. Conclusions:A dynamic nomogram for abnormal bone mass in ESRD patients is constructed with good predictive performance based on the prediction model, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors and assist physicians in making a personalized diagnosis for patients.

Objective:To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths.Methods:The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results:(1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer ( P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage ( HR=1.882, 95% CI: 1.305-2.716), LNM ( HR=2.178, 95% CI: 1.483-3.200) and UCI ( HR=3.650, 95% CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage ( HR=2.500, 95% CI: 1.580-3.956), LNM ( HR=2.053, 95% CI: 1.309-3.218), UCI ( HR=3.984, 95%C I: 1.917-8.280), PVM ( HR=3.235, 95% CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% ( P=0.794), and the 5-year OS were 90.8% and 89.3% ( P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions:Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Objective:To evaluate the clinical outcome of a special physeal sparing knee prosthesis for pediatric distal femoral osteosarcoma regarding the functional outcome, retention of the growth potential of the proximal tibia, and postoperative complications.Methods:A retrospective study was conducted to review 37 pediatric patients with osteosarcoma of distal femur who were treated in a single musculuskeletal tumor center between August 2015 and January 2019. Among them, 21 were boys and 16 were girls, aged from 5 to 12 years at the time of operation, with an average age of 9.1±2.1 years and the height of 115 to 160 cm, with an average of 140±10 cm. Tumor resection of distal femur was performed and the bone defect was reconstructed by a special hinged knee prosthesis which can preserve the proximal tibial epiphyseal plate. Demographic data was recorded. Overall leg length and tibial length was assessed by full-length standing anteroposterior radiographs of bilateral lower extremity with the patella pointing anteriorly preoperativelly and postoperativelly at each follow up. And the growth potential of the affected proximal tibia was calculated by comparing with the preoperative length of tibia. Meanwhile, the functional outcome was assessed by using the Musculoskeletal Tumor Society (MSTS) system, and the postoperative complications were analysed.Results:All patients underwent the tumor resection and reconstruction operation successfully. The average operation duration was 143±41 minutes, ranging 90 to 250 minutes. The average intraoperative blood loss was 314±397 ml, ranging 30 to 2 200 ml. The patients were followed up for 24 to 64 months, averaging 42.3±12.1 months. The postoperative knee range of motion was 100-130 degrees, with an average of 115.6±7.2 degrees. The postoperative MSTS score was 23-30, with an average of 26.7±1.6. To the last follow-up, the limb length discrepancy of the lower limb was 1.3 to 10 cm, and the length of the tibia was shortened from 0 to 3.8 cm compared with the opposite side, with an average of 1.3±1.0 cm. The growth percentage of the proximal tibial epiphysis on the affected side was 30% to 100%, with an average of 70%±17%. Totally, 13 patients suffered postoperative complication, the overall incidence of complications was 35% (13/37), and prosthesis-related complications were 16% (6/37). Three patients with wound dehiscence were managed by debridement and antibiotics. Radiographs revealed femoral stem loosening in a single patient 3 years after the initial operation and then the prosthesis was converted to an adult tumor knee endoprosthesis. Two cases experienced breakage of the femoral stem at 30 and 33 months, respectively, due to an accidental injury. They received revision surgery, and a new femoral prosthesis component was replaced. One patient developed femoral stem breakage at 10 months after surgery due to fatigue fracture, which treated with revision surgery. Tumor recurrence occurred in 6 patients. Among them, tumor recurrence in soft tissue occurred in 4 patients, and treated with regional resection without further recurrence. The other 2 patients experienced tumor recurrence at the distal femoral site, and treated with resection and prosthetic revision.Conclusion:The physeal sparing pediatric knee prosthesis can preserve the growth potential of the proximal tibial epiphyseal plate with good postoperative function and low incidence of prosthesis complications. Therefore, it can be an alternativeespecially for skeletally immature patients with distal femur osteosarcoma.

ObjectiveTo visually analyze the current status, hot spots and frontiers of the researches on transcranial magnetic stimulation for stroke in recent five years. MethodsLiterature related to transcranial magnetic stimulation for stroke were retrieved from the Web of Science Core Collection from January 1, 2018 to December 31, 2022, and a visualized analysis was performed using CiteSpace 6.1.R6 software. ResultsThe number of published papers increased year by year, the most prolific author was Abo Masahiro, the country with the largest number of articles was China, and Sun Yat-sen University published the most papers. The hot keywords were cerebral cortex, functional magnetic resonance imaging, cortical excitability, plasticity, etc. The top five keywords of bursting strength were unilateral spatial neglect, poststroke, neuropathic pain, cortical plasticity, and trancallosal inhibition. ConclusionThe popularity of studies on transcranial magnetic stimulation in the treatment of stroke is increasing year by year. In the future, attention can be paid to the therapeutic effect of transcranial magnetic stimulation on unilateral spatial neglect, neuropathic pain, etc. Additionally, the influence of transcranial magnetic stimulation on cortical plasticity can be further studied.

ObjectiveTo explore the effects of different intensity of wearable lower limb rehabilitation robot-assisted training on walking function, lower limb motor function, balance function and functional independence of stroke patients. MethodsFrom November, 2021 to December, 2022, 60 stroke patients hospitalized in Beijing Bo'ai Hospital were randomly divided into control group (n = 20), observation group 1 (n = 20) and observation group 2 (n = 20). All the groups received routine rehabilitation, while the control group received routine walking training 30 minutes a day, the observation group 1 received wearable lower limb rehabilitation robot-assisted training 30 minutes a day, and the observation group 2 received wearable lower limb rehabilitation robot-assisted training 60 minutes a day, for four weeks. They were assessed with Functional Ambulation Category scale (FAC), Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Berg Balance Scale (BBS) and Rivermead Mobility Index (RMI) before and after treatment. ResultsOne case in the observation group 1 and three cases in the observation group 2 dropped down. The FAC, FMA-LE, BBS and RMI scores improved in all the three groups after treatment (|Z| > 3.448, |t| > 8.102, P < 0.001), and there was no significant difference in all the indexes among the three groups (|H| < 4.643, F = 1.454, P > 0.05); however, the improvement of BBS score was more in the observation group 1 than in the control group (P < 0.05), and the improvement of all the indexes was more in the observation group 2 than in the control group (P < 0.05). ConclusionThe wearable lower limb rehabilitation robot-assisted training may promote the recovery of walking function, lower limb motor function, balance function and functional independence of stroke patients, and high-intensity training seems to be more effective.

Objective:To investigate the efficacy of 3D-printed segmental tumor prosthesis for reconstruction of bone defects after resection of weight-bearing long bone tumors in the lower extremity.Methods:A total of 71 patients who received 3D-printed segmental metal tumor prosthesis for reconstruction of bone defects from August 2015 to August 2021 at the Musculoskeletal Tumor Center of Peking University People's Hospital were retrospectively analyzed. There were 40 males and 31 females, aged 23.08±18.52 years (range, 10-63 years). Tumor types: 49 cases of osteosarcoma, 9 cases of Ewing sarcoma, 3 cases of chondrosarcoma, 3 cases of synovial sarcoma, 2 cases of pleomorphic undifferentiated sarcoma, 2 cases of rhabdomyosarcoma, 2 cases of bone metastasis, and 1 case of low-grade malignant tumor of mesenchymal origin. Ennecking stage of bone tumor: 19 cases of stage III, 52 cases of stage IIb. Tumor location: femur 43 cases, tibia 28 cases. Operative time, intraoperative bleeding, patient survival and postoperative complications were recorded. Kaplan-Meier curves for prosthetic survival were plotted. The osseointegration at the prothesis-bone interface was determined by combination of clinical presentation and imaging. Limb function scores were evaluated using the Musculoskeletal Tumor Society (MSTS) 93 function score.Results:All 71 patients successfully completed the operation and were followed up for 24.4±13.2 months (range, 6.6-65.4 months). At the last follow-up, 50 patients survived without disease, 12 survived with the disease, and the remaining 9 cases died with disease. A total of 11 cases showed prosthesis failure, including 1 case of aseptic loosening, 3 cases of screw breakage or periprosthetic fracture, 1 case of periprosthetic infection, and 6 cases of tumor progression involving the prosthesis. The Kaplan-Meier curve showed that the 1-year, 3-year and 5-year survival rates of prosthesis were 94.2%±2.8%, 86.1%±4.7% and 79.5%±9.2%, respectively. 62 patients received functional follow-up, and the MSTS93 functional score at the last follow-up was 23.95±5.03 points (range, 10-30 points), with an excellent rate of 90% (56/62). The score of femoral prosthesis was 24.63±4.97 points (range, 13-30 points) and the score of tibial prosthesis was 23.29±5.09 points (range, 10-29).Conclusion:3D-printed segmental tumor prosthesis for reconstruction of bone defect after resection of weight-bearing long bone tumors in the lower extremity has a relative high survival rate, a low incidence of prosthetic complications, and a good recovery of function, and it can be used as an option for the postoperative reconstruction of bone tumors in weight-bearing bones of the lower extremity.

ObjectiveTo investigate the effects of an intelligent aerobic bicycle training on lower limb motor function, cardiopulmonary function and activities of daily living (ADL) in patients with ischemic stroke at different courses. MethodsFrom November, 2019 to November, 2021, 138 ischemic stroke patients were stratified-randomly divided into control group (n = 69) and experimental group (n = 69). All the patients received medication and routine rehabilitation training, and the experimental group additionally received intelligent aerobic bicycle training, for eight weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremities (FMA-LE), peak oxygen uptake (VO₂peak), Six-minute Walk Test (6MWT) and modified Barthel Index (MBI) before, and four weeks and eight weeks after treatment. ResultsThe performances of FMA-LE, VO₂peak, 6MWT and MBI improved in both groups after treatment (|t| > 6.763, P < 0.001), and improved more in the experimental group than in the control group (|t| > 2.439, P < 0.05). For the patients beginning training less than one month after stroke, the performances of FMA-LE, VO₂peak and 6MWT improved more in the experimental group than in the control group (|t| > 2.036, P < 0.05); for those during one to three months, the performances of 6MWT and MBI improved more (|t| > 2.005, P < 0.05); for those during three to six months, the performances of all the tests were not significantly different (|t| < 1.303, P > 0.05). ConclusionIntelligent aerobic bicycle training may improve the lower limb motor function, cardiopulmonary function and ADL for patients with ischemic stroke, especially intervening earlier.

Objective:To investigate the application value of digital single-operator peroral cholangioscopy on the preoperative evaluation of extrahepatic cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 172 patients with extrahepatic cholangiocarcinoma who were admitted to the First Affiliated Hospital of Army Medical University from December 1, 2017 to April 1, 2022 were collected. There were 91 males and 81 females, aged 65(range, 45?68)years. Of 172 patients, 36 cases undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the experimental group, and 136 cases not undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the control group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) surgical conditions. Propensity score matching was done by the 1:1 nearest neighbor matching method and caliper setting as 0.02. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1,Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 172 patients, 60 cases were successfully matched, including 30 cases in the experiment group and 30 cases in the control group, respectively. Before propensity score matching, cases with or without preoperative bile drainage were 27, 9 in the experiment group, versus 62, 74 in the control group, showing a significant difference between the two groups ( χ2=9.86, P<0.05). The above indicators were 23, 7 in the experiment group, and 23, 7 in the control group after propensity score matching, showing no significant difference between the two groups ( χ2=0.00, P>0.05). The elimination of preoperative bile drainage confounding bias ensured comparability between the two groups. (2) Surgical conditions. After propensity score matching, there were 10 cases and 0 case without surgery in the two groups. Cases undergoing radical operation including R 0, R 1, R 2 resection were 16, 0, 4 in the experiment group, versus 18, 6, 6 in the control group, showing a significant difference between the two groups ( χ2=6.85, P<0.05). Conclusions:Preoperative digital single-operator peroral cholangioscopy exami-nation can improve the R 0 resection rate of extrahepatic cholangiocarcinoma.