1.Wenshen Tongdu Recipe Promotes the Recovery of Rats with Spinal Cord Injury by Activating Autophagy through the Akt/mTOR Signaling Pathway and Regulating Microglial Polarization
Haoheng ZHANG ; Sixian CHEN ; Yang GUO ; Ruihua ZHAO ; Muzhe LI ; Xiaoxian SUN ; Yong MA ; Yunfei YU ; Mao WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):904-913
OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.
2.Selective hemivertebrae resection for lumbosacral combined with thoracolumbar/lumbar hemimetameric segmental shift deformities: efficacy and complications
Jie ZHOU ; Song LI ; Kai SUN ; Zhen LIU ; Yong QIU ; Zezhang ZHU ; Saihu MAO
Chinese Journal of Orthopaedics 2025;45(9):542-551
Objective:To explore a selective resection strategy for combined lumbosacral hemivertebra (LSHV) and thoracolumbar hemivertebra/lumbar hemivertebra (TLHV/LHV) double-balanced hemivertebra deformities.Methods:A retrospective analysis was conducted on 21 patients aged over 10 years with lumbosacral and thoracolumbar or lumbar combined hemimetameric segmental shift (HMMS) deformities who underwent surgery at Nanjing Drum Tower Hospital between May 2009 and October 2022. The cohort included 7 males and 14 females, with a mean surgical age of 21.5±10.9 years (range: 12-55 years) and a mean follow-up duration of 32.8±15.9 months (range: 24-74 months). Patients were divided into two groups based on preoperative coronal balance: the balanced group (Type A) and the unbalanced group (Type C). Radiographic parameters, including the major Cobb angle, lumbosacral take-off angle, kyphotic angle, coronal balance distance (CBD), and the deviation of the upper instrumented vertebra (UIV), were measured preoperatively, postoperatively, and at the final follow-up. Surgical complications were also recorded.Results:Of the 21 patients, 11 were classified as preoperatively balanced, and 10 as unbalanced. The deformity angular ratio of thoracolumbar to lumbosacral curves was significantly higher in the balanced group than in the unbalanced group (0.9±0.3 vs. 0.6±0.2; t=2.143, P=0.045). The preoperative main curve Cobb angles in the balanced and imbalanced groups were 71.3°±22.3° and 58.6°±8.2°, respectively. One week postoperatively, these angles were reduced to 38.4°±17.6° and 31.3°±5.6°, and were maintained at 40.0°±18.1° and 32.6°±5.6° at the final follow-up, all differences were statistically significant ( P<0.05). The preoperative lumbosacral take-off angles were 37.5°±9.1° in the balanced group and 36.7°±7.7° in the imbalanced group, which decreased to 18.4°±9.4° and 19.2°±5.5° at 1 week postoperatively, and remained at 19.4°±10.1° and 19.6°±5.8° at the final follow-up. These changes were also statistically significant ( P<0.05). In the balanced group, the UIV tilt angle, the CBD and the deviation of the UIV, were all significantly reduced compared to preoperative values ( P<0.05). Among the 21 patients, LSHV resection was performed in 15 cases, and TLHV/LHV resection was performed in 7 cases. Among the 15 patients with kyphosis, TLHV/LHV resection was performed in 6 cases. In the balanced group, 9 patients maintained type A postoperatively, including 4 patients with LSHV resection, 2 with TLHV/LHV resection, 2 with both LSHV and TLHV/LHV resection, 1 without resection of both hemivertebra. Two patients in the balanced group who underwent TLHV/LHV resection experienced postoperative deterioration to type C. In the unbalanced group, 8 cases with LSHV resection improved to type A, while 1 case with LSHV resection and 1 case with neither resection maintained C-type. In the LSHV resection group, CBD improved from 29.8±15.2 mm to 13.9±5.7 mm postoperatively and remained stable at 14.6±8.6 mm at final follow-up. Only 1 patient in this group experienced worsened coronal imbalance. In contrast, in the non-LSHV resection group, CBD worsened from 17.2 ± 8.7 mm to 19.7±12.1 mm postoperatively, progressing further to 20.5±13.0 mm at follow-up. Three patients in this group had worsening coronal imbalance, and 2 required revision surgery. Reported complications included 3 cases of internal fixation fracture, 1 case of proximal junctional kyphosis, and 1 case of acute incision infection. Conclusions:Effective resection of lumbosacral hemivertebrae is the preferred selective strategy, particularly for patients with preoperative coronal imbalance, as it significantly reduces the risk of worsening coronal imbalance and internal fixation-related complications. However, selective resection involving only TLHV or LHV without addressing LSHV in preoperatively balanced patients may increase the risk of postoperative coronal imbalance.
3.Surgical efficacy evaluation of NF1-related dystrophic lumbosacral deformity: comparative analysis between pelvic and non-pelvic fixation
Song LI ; Zezhang ZHU ; Jie ZHOU ; Saihu MAO ; Shuqi SUN ; Zhen LIU ; Benlong SHI ; Xu SUN ; Jun QIAO ; Yong QIU
Chinese Journal of Orthopaedics 2025;45(9):604-612
Objective:To analyze the selection of internal fixation methods, surgical outcomes, and complications in patients with Neurofibromatosis Type 1 (NF1) accompanied by dystrophic lumbosacral deformities, and to evaluate the indications for pelvic fixation.Methods:A retrospective analysis was conducted on 21 patients with NF1 and associated dystrophic lumbosacral malformations (L 4 to sacrum) who underwent spinal deformity correction surgery at Nanjing Drum Tower Hospital from January 2009 to November 2022. The cohort included 11 males and 10 females, with a mean surgical age of 15.4±4.7 years (range, 7-24 years). Patients were divided into two groups based on whether pelvic fixation was performed: 10 patients in the non-pelvic fixation group (NP group) and 11 in the pelvic fixation group (P group), where fixation involved second sacral alar-iliac (S 2AI) screws or iliac screws. Radiographic parameters, including the Cobb angle of the lumbosacral fractional curve, main curve, and focal kyphosis, were compared preoperatively, postoperatively, and at the last follow-up. Results:The NP group had a significantly lower mean age (13.2±4.9 years) compared to the P group (17.5±3.5 years; t=2.287, P=0.034). Spinal instability (rotational subluxation or spondylolisthesis) due to dystrophic changes was observed in 2 patients in the NP group and 8 in the P group, a statistically significant difference (χ 2=5.838, P=0.030). In the P group, five patients underwent unilateral fixation and six underwent bilateral fixation. Implant types included 2 cases with iliac screws, 1 case with iliac screws plus S 2AI, and 8 cases with S 2AI screws alone. The utilization rate of hooks was significantly higher in the NP group (12.6%±11.5%) compared to the P group (3.5%±6.9%; t=2.230, P=0.038). The preoperative Cobb angle of the lumbosacral fractional curve was significantly smaller in the NP group (13.8°±9.0°) than in the P group (25.5°±13.9°; t=2.228, P=0.039). Postoperatively, the angles were corrected to 6.3°±6.1° and 6.4°±5.3°, respectively ( t=0.901, P=0.969), with correction rates of 57.3%±13.6% and 74.1%±17.8% ( t=2.369, P=0.029). At final follow-up, the angles remained stable (6.6°±6.6° vs. 6.3°±4.8°; t=0.116, P=0.909). For the main curve, preoperative Cobb angles were 52.5°±15.1° (NP) and 61.1°±16.9° (P; t=1.200, P=0.246), corrected to 31.3°±13.8° and 28.0°±8.4°, respectively ( t=0.646, P=0.526). Correction rates were 41.3%±13.0% in the NP group and 53.2%±11.6% in the P group ( t=2.206, P=0.037). At the final follow-up, these values were 32.4°±14.2° and 31.7°±10.3° ( t=0.133, P=0.896). Focal kyphosis, seen in 9 patients, was corrected from 19.7°±10.9° preoperatively to -13.6°±9.5° postoperatively, and remained at -14.1°±9.6° at the final follow-up ( F=33.547, P<0.001). Multi-rod systems were used in 6 cases (NP group) and 7 cases (P group), with no significant difference (χ 2=0.153, P=0.926). Two patients in the NP group developed coronal decompensation three years postoperatively, and one required revision surgery. In the P group, rod breakage occurred in 3 patients, two of whom underwent revision. Conclusions:Dystrophic rotational subluxation or spondylolisthesis of the lumbosacral spine is a primary indication for pelvic fixation in patients with NF1-associated deformities. However, complications related to internal fixation remain common. The combined use of a multi-rod screw-hook hybrid system, particularly when extending across the lumbosacral region, may reduce the risk of instrumentation failure.
4.Development of a visualizable machine learning model for mechanical complication risk in adult spinal deformity surgery
Jie LI ; Zhen TIAN ; Zhong HE ; Xiaodong QIN ; Jun QIAO ; Saihu MAO ; Benlong SHI ; Yong QIU ; Zezhang ZHU ; Zhen LIU
Chinese Journal of Orthopaedics 2025;45(17):1137-1146
Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.
5.Optimized lipid nanoparticles enable effective CRISPR/Cas9-mediated gene editing in dendritic cells for enhanced immunotherapy.
Kuirong MAO ; Huizhu TAN ; Xiuxiu CONG ; Ji LIU ; Yanbao XIN ; Jialiang WANG ; Meng GUAN ; Jiaxuan LI ; Ge ZHU ; Xiandi MENG ; Guojiao LIN ; Haorui WANG ; Jing HAN ; Ming WANG ; Yong-Guang YANG ; Tianmeng SUN
Acta Pharmaceutica Sinica B 2025;15(1):642-656
Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLANmCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.
6.Wenshen Tongdu Recipe Promotes the Recovery of Rats with Spinal Cord Injury by Activating Autophagy through the Akt/mTOR Signaling Pathway and Regulating Microglial Polarization
Haoheng ZHANG ; Sixian CHEN ; Yang GUO ; Ruihua ZHAO ; Muzhe LI ; Xiaoxian SUN ; Yong MA ; Yunfei YU ; Mao WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):904-913
OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.
7.Detection rate and associated factors of knee bone marrow edema-like signals in amateur marathon runners
Yong CHEN ; Jie LIU ; Li ZHANG ; Xinmiao MAO ; Wanzhen YAO ; Jing ZHOU ; Jianping DING ; Shinong PAN ; Jian ZHAO ; Yanjing ZHANG
Chinese Journal of General Practitioners 2025;24(10):1269-1275
Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.
8.Selective hemivertebrae resection for lumbosacral combined with thoracolumbar/lumbar hemimetameric segmental shift deformities: efficacy and complications
Jie ZHOU ; Song LI ; Kai SUN ; Zhen LIU ; Yong QIU ; Zezhang ZHU ; Saihu MAO
Chinese Journal of Orthopaedics 2025;45(9):542-551
Objective:To explore a selective resection strategy for combined lumbosacral hemivertebra (LSHV) and thoracolumbar hemivertebra/lumbar hemivertebra (TLHV/LHV) double-balanced hemivertebra deformities.Methods:A retrospective analysis was conducted on 21 patients aged over 10 years with lumbosacral and thoracolumbar or lumbar combined hemimetameric segmental shift (HMMS) deformities who underwent surgery at Nanjing Drum Tower Hospital between May 2009 and October 2022. The cohort included 7 males and 14 females, with a mean surgical age of 21.5±10.9 years (range: 12-55 years) and a mean follow-up duration of 32.8±15.9 months (range: 24-74 months). Patients were divided into two groups based on preoperative coronal balance: the balanced group (Type A) and the unbalanced group (Type C). Radiographic parameters, including the major Cobb angle, lumbosacral take-off angle, kyphotic angle, coronal balance distance (CBD), and the deviation of the upper instrumented vertebra (UIV), were measured preoperatively, postoperatively, and at the final follow-up. Surgical complications were also recorded.Results:Of the 21 patients, 11 were classified as preoperatively balanced, and 10 as unbalanced. The deformity angular ratio of thoracolumbar to lumbosacral curves was significantly higher in the balanced group than in the unbalanced group (0.9±0.3 vs. 0.6±0.2; t=2.143, P=0.045). The preoperative main curve Cobb angles in the balanced and imbalanced groups were 71.3°±22.3° and 58.6°±8.2°, respectively. One week postoperatively, these angles were reduced to 38.4°±17.6° and 31.3°±5.6°, and were maintained at 40.0°±18.1° and 32.6°±5.6° at the final follow-up, all differences were statistically significant ( P<0.05). The preoperative lumbosacral take-off angles were 37.5°±9.1° in the balanced group and 36.7°±7.7° in the imbalanced group, which decreased to 18.4°±9.4° and 19.2°±5.5° at 1 week postoperatively, and remained at 19.4°±10.1° and 19.6°±5.8° at the final follow-up. These changes were also statistically significant ( P<0.05). In the balanced group, the UIV tilt angle, the CBD and the deviation of the UIV, were all significantly reduced compared to preoperative values ( P<0.05). Among the 21 patients, LSHV resection was performed in 15 cases, and TLHV/LHV resection was performed in 7 cases. Among the 15 patients with kyphosis, TLHV/LHV resection was performed in 6 cases. In the balanced group, 9 patients maintained type A postoperatively, including 4 patients with LSHV resection, 2 with TLHV/LHV resection, 2 with both LSHV and TLHV/LHV resection, 1 without resection of both hemivertebra. Two patients in the balanced group who underwent TLHV/LHV resection experienced postoperative deterioration to type C. In the unbalanced group, 8 cases with LSHV resection improved to type A, while 1 case with LSHV resection and 1 case with neither resection maintained C-type. In the LSHV resection group, CBD improved from 29.8±15.2 mm to 13.9±5.7 mm postoperatively and remained stable at 14.6±8.6 mm at final follow-up. Only 1 patient in this group experienced worsened coronal imbalance. In contrast, in the non-LSHV resection group, CBD worsened from 17.2 ± 8.7 mm to 19.7±12.1 mm postoperatively, progressing further to 20.5±13.0 mm at follow-up. Three patients in this group had worsening coronal imbalance, and 2 required revision surgery. Reported complications included 3 cases of internal fixation fracture, 1 case of proximal junctional kyphosis, and 1 case of acute incision infection. Conclusions:Effective resection of lumbosacral hemivertebrae is the preferred selective strategy, particularly for patients with preoperative coronal imbalance, as it significantly reduces the risk of worsening coronal imbalance and internal fixation-related complications. However, selective resection involving only TLHV or LHV without addressing LSHV in preoperatively balanced patients may increase the risk of postoperative coronal imbalance.
9.Surgical efficacy evaluation of NF1-related dystrophic lumbosacral deformity: comparative analysis between pelvic and non-pelvic fixation
Song LI ; Zezhang ZHU ; Jie ZHOU ; Saihu MAO ; Shuqi SUN ; Zhen LIU ; Benlong SHI ; Xu SUN ; Jun QIAO ; Yong QIU
Chinese Journal of Orthopaedics 2025;45(9):604-612
Objective:To analyze the selection of internal fixation methods, surgical outcomes, and complications in patients with Neurofibromatosis Type 1 (NF1) accompanied by dystrophic lumbosacral deformities, and to evaluate the indications for pelvic fixation.Methods:A retrospective analysis was conducted on 21 patients with NF1 and associated dystrophic lumbosacral malformations (L 4 to sacrum) who underwent spinal deformity correction surgery at Nanjing Drum Tower Hospital from January 2009 to November 2022. The cohort included 11 males and 10 females, with a mean surgical age of 15.4±4.7 years (range, 7-24 years). Patients were divided into two groups based on whether pelvic fixation was performed: 10 patients in the non-pelvic fixation group (NP group) and 11 in the pelvic fixation group (P group), where fixation involved second sacral alar-iliac (S 2AI) screws or iliac screws. Radiographic parameters, including the Cobb angle of the lumbosacral fractional curve, main curve, and focal kyphosis, were compared preoperatively, postoperatively, and at the last follow-up. Results:The NP group had a significantly lower mean age (13.2±4.9 years) compared to the P group (17.5±3.5 years; t=2.287, P=0.034). Spinal instability (rotational subluxation or spondylolisthesis) due to dystrophic changes was observed in 2 patients in the NP group and 8 in the P group, a statistically significant difference (χ 2=5.838, P=0.030). In the P group, five patients underwent unilateral fixation and six underwent bilateral fixation. Implant types included 2 cases with iliac screws, 1 case with iliac screws plus S 2AI, and 8 cases with S 2AI screws alone. The utilization rate of hooks was significantly higher in the NP group (12.6%±11.5%) compared to the P group (3.5%±6.9%; t=2.230, P=0.038). The preoperative Cobb angle of the lumbosacral fractional curve was significantly smaller in the NP group (13.8°±9.0°) than in the P group (25.5°±13.9°; t=2.228, P=0.039). Postoperatively, the angles were corrected to 6.3°±6.1° and 6.4°±5.3°, respectively ( t=0.901, P=0.969), with correction rates of 57.3%±13.6% and 74.1%±17.8% ( t=2.369, P=0.029). At final follow-up, the angles remained stable (6.6°±6.6° vs. 6.3°±4.8°; t=0.116, P=0.909). For the main curve, preoperative Cobb angles were 52.5°±15.1° (NP) and 61.1°±16.9° (P; t=1.200, P=0.246), corrected to 31.3°±13.8° and 28.0°±8.4°, respectively ( t=0.646, P=0.526). Correction rates were 41.3%±13.0% in the NP group and 53.2%±11.6% in the P group ( t=2.206, P=0.037). At the final follow-up, these values were 32.4°±14.2° and 31.7°±10.3° ( t=0.133, P=0.896). Focal kyphosis, seen in 9 patients, was corrected from 19.7°±10.9° preoperatively to -13.6°±9.5° postoperatively, and remained at -14.1°±9.6° at the final follow-up ( F=33.547, P<0.001). Multi-rod systems were used in 6 cases (NP group) and 7 cases (P group), with no significant difference (χ 2=0.153, P=0.926). Two patients in the NP group developed coronal decompensation three years postoperatively, and one required revision surgery. In the P group, rod breakage occurred in 3 patients, two of whom underwent revision. Conclusions:Dystrophic rotational subluxation or spondylolisthesis of the lumbosacral spine is a primary indication for pelvic fixation in patients with NF1-associated deformities. However, complications related to internal fixation remain common. The combined use of a multi-rod screw-hook hybrid system, particularly when extending across the lumbosacral region, may reduce the risk of instrumentation failure.
10.Development of a visualizable machine learning model for mechanical complication risk in adult spinal deformity surgery
Jie LI ; Zhen TIAN ; Zhong HE ; Xiaodong QIN ; Jun QIAO ; Saihu MAO ; Benlong SHI ; Yong QIU ; Zezhang ZHU ; Zhen LIU
Chinese Journal of Orthopaedics 2025;45(17):1137-1146
Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.

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