Ziming Zhang

Purpose: The aim of this study was to evaluate the surgical outcomes of proximal femoral bone cysts in pediatric patients.Methods: We retrospectively analyzed 41 pediatric patients (31 males and 10 females, mean age 7.47 ± 2.67 years, range 2.03–14.67 years) diagnosed with proximal femoral bone cysts treated at a single institute between March 2009 and November 2021. Data included demographics, preoperative details, intraoperative conditions, surgical techniques, postoperative outcomes, recurrence, and complications.Results: Of the participants, 68% presented with simple bone cysts and 32% with aneurysmal bone cysts. Prior to surgery, 32% exhibited pathological fractures. Surgical methods included lesion curettage, defect filling using allograft bone and Minimally-Invasive Injectable Graft ×3, and varied fixation techniques. Postoperative recurrence (17%) was associated with cyst location between the capital femoral epiphysis and the linea intertrochanterica (P = 0.010). At the final assessment (mean follow-up: 26.51 ± 18.99 months), all showed radiological bony union with 93% rated as “good” and 7% as ‘fair’ based on Ratliff hip scores. Complications arose in 20% of patients, significantly correlated with prior pathological fractures (P = 0.007) and their association with the linea intertrochanterica (P = 0.004). Those with fractures reported higher intraoperative blood loss (P = 0.015) and longer surgery durations (P = 0.012) compared to those without.Conclusion: Treating pediatric proximal femoral bone cysts using techniques such as lesion curettage, defect filling, and selective internal fixation yields favorable outcomes. The presence of pathological fractures can prolong surgical time, increase intraoperative blood loss, and elevate postoperative complication risks. Hence, early surgical intervention for these cysts is recommended to prevent fractures.

Background: Osteosarcoma (OS) mainly happens in children and youths. Surgery, radiotherapy and chemotherapy are the common therapies for osteosarcoma treatment but all their anti-tumor effects are limited. In recent years, a new cellular therapy, CAR-T, a cellular immunotherapy with genetically engineered T cells bearing chimeric antigen receptor targeting specific tumor-associated antigen, has been proved to be an effective therapy against acute lymphoblastic leukemia. Thus, CAR-T is a potentially effective therapy for osteosarcoma treatment. Methods: A CAR gene targeting B7-H3 antigen was constructed into lentiviral vector through molecular biology techniques. Then, the CAR gene was transferred to T cells through lentiviral delivery system, and the CAR-T cells were largely expanded using in vitro culture technology. The in vitro anti-tumor effect of CAR-T cells was evaluated through Real Time Cell Analysis system (RTCA) and ELISA assay. The in vivo anti-tumor capabilities of CAR-T cells were evaluated using the patient-derived xenografts (PDX) model of osteosarcoma. Results: The third-generation CAR-T cells we constructed could target the B7-H3 antigen, and the phenotype of CAR-T cells was consistent with normal T cells; The CAR-T cells showed superior antitumor effects both in vitro and in vivo. Conclusion: Our study showed that B7-H3 targeted CAR-T cells had high anti-tumor efficacy against osteosarcoma both in vitro and in vivo, which proved that B7-H3 targeted CAR-T therapy is potentially effective for osteosarcoma treatment.

Objective: The current study aims to conduct a quantitative dynamic analysis of hip morphology using a computer-assisted design (CAD) model to evaluate the combined pelvic and femoral osteotomies in the treatment of Legg-Calvé-Perthes disease (LCPD).Materials and methods: CAD models of patients with unilateral LCPD treated by combined pelvic and proximal femoral osteotomies were established based on the data of CT scan, on which morphological parameters were measured. Shape difference analysis of normal hips was adopted to locate the most apparent displacement and the main strain on the surface of the proximal femur.Results: Fifteen patients were included, and the mean age of receiving operation was 6.63 years old. There were 10 hips rated as Herring type C, and the rest were type B. Compared with the normal side, the affected hip joints have a longer distance between femoral head and acetabular sphere. The difference of coverage area of the femoral head surface and femoral head volume between the affected and normal sides was bigger compared with the preoperative model, respectively. The changes in the acetabular radius and the area of the surface were not apparent, pre-, and post-operatively. The displacement was mainly on superior and lateral superior portions of the femoral head where the stresses were concentrated.Conclusion: Combined pelvic and femoral osteotomies could effectively improve the superior and superior–posterior area of acetabulum containment with increased femoral head volume. CAD model and shape difference analysis can provide a better understanding of deformations of LCPD and more information for surgical planning and evaluation of treatment outcomes.

Inflammatory diseases decrease the extracellular environmental pH. However, whether proton-activated G protein-coupled receptors (GPCRs) can regulate the development of osteoarthritis (OA) is largely unknown. In this study, we report that proton-activated GPR4 is essential for OA development. We found a marked increase in expression of the proton-activated GPR4 in human and mouse OA cartilage. Lentivirus-mediated overexpression of GPR4 in mouse joints accelerated the development of OA, including promotion of articular cartilage damage, synovial hyperplasia, and osteophyte formation, while Gpr4 knockout effectively attenuated the development of posttraumatic and aging-associated OA in mice. We also found that inhibition of GPR4 with the antagonist NE52-QQ57 ameliorated OA progression in mice, promoted extracellular matrix (ECM) production, and protected cartilage from degradation in human articular cartilage explants. Moreover, GPR4 overexpression upregulated matrix-degrading enzymes’ expression and inflammation factors under pro-inflammatory and slightly acidic conditions. Mechanistically, GPR4 suppressed chondrocyte differentiation and upregulated cartilage homeostasis through NF-κB/MAPK signaling activation by regulating CXCR7/CXCL12 expression. Together, our results take the lead to illustrate that proton-activated GPCR acts as a key regulator for OA pathogenesis in vivo, and support that GPR4 could be a promising therapeutic target for OA treatment.

Background: Temporary hemiepiphysiodesis (TH) using an eight-Plate implant is one of the most common surgeries used for the correction of coronal angular deformities around the knee in adolescents. However, few studies have focused on children aged less than 10 years treated with TH using an eight-Plate implant. The purpose of this study was to investigate the efficacy, correction velocity, and complications of TH with an eight-Plate implant as well as the occurrence of rebound and risk factors in this population. Methods: This retrospective study included a total of 135 physes (101 knees) from 66 children (mean age of 4.69 years old, range from 1 to 10 years old) who underwent TH with an eight-Plate implant to correct coronal genu angular deformities in our hospital. Related clinical factors were recorded and analysed by multivariable linear and logistic regression models. Results: The mean deformity correction period was 13.26 months, and the mean follow-up after eight-Plate removal was 12.71 months. In all, 94.06% (95/101 knees) of the genu angular deformities were completely corrected. Non-idiopathic genu angular deformity was found to be an independent risk factor for deformity correction failure (odds ratio (OR) = 2.47). The femoral correction velocity was significantly higher than the tibial correction velocity (1.28° vs. 0.83° per month, p < 0.001). After adjustment for other factors, younger children had higher correction velocities in the distal femur; however, genu valgum and idiopathic deformities were associated with higher correction velocities in the proximal tibia. In addition, we found three (3/101, 2.97%) knees with genu valgum that experienced rebound after removal of the eight-Plate, while five (5/101, 4.95%) knees with non-idiopathic genu angular deformity experienced screw loosening. No other complications were found, and non-idiopathic deformity was the only risk factor for complications (OR = 3.96). No risk factor was found for rebound in our study. Conclusions: TH using an eight-Plate implant is an effective procedure for coronal genu angular deformities with a low incidence of complications and rebound in patients younger than 10 years old. For this population, TH using an eight-Plate should be considered as soon as the deformity stops responding to conservative treatments. The parents of children younger than 10 years of age with non-idiopathic deformities should be informed preoperatively that the deformity may be prone to correction failure or screw loosening after eight-Plate implantation.

Background: It remains controversial whether the older age to perform closed reduction (CR) procedure for developmental dysplasia of the hip (DDH), the higher incidence of complications. The aim of this study is to evaluate the midterm outcome of CR for DDH among different age groups, and to analyze and identify risk factors for the failure of this procedure.Methods: Clinical data of 107 DDH patients, who received CR, were retrospectively reviewed. Data were divided into three groups according to initial treatment age (Group I: younger than 12 months; Group II: 12 months to less or equal to18 months; Group III: older than 18 months). The presence of avascular necrosis (AVN), residual acetabular dysplasia (RAD), re-dislocation, and further surgeries (FS) were observed. The risk factors were identified for those outcomes aforementioned using univariable logistic regression models. For identified risk factor age, pre-op acetabular index (AI) and post-op AI, their prediction of CR failure were evaluated by receiver operating characteristics curve (ROC).Results: A total of 107 patients (156 hips) undergoing CR procedure were evaluated with a median age at initial reduction of 13.0 ± 5.4 months (range, 4 to 28 mo). Mean follow-up time in this study was 6.7 ± 0.8 years (range, 3–8 years). The incidence of AVN, RAD and re-dislocation was 15.4% (24/156), 17.3% (27/156) and 14.7% (23/156) respectively. For AVN, RAD and re-dislocation, the significant risk factors are pre-op IHDI IV (p = 0.033), age ≥ 18 months (p = 0.012), and pre-op IHDI IV (p = 0.004) and walking (p = 0.011), respectively. The areas under the ROC curve of each type of failures were 0.841 (post-op AI), 0.688 (pre-op AI) and 0.650 (age).Conclusions: Severe DDH patients older than 18 months with CR procedure may result in a high risk of RAD complication. Re-dislocation is significantly associated with pre-op IHDI IV and walking. Patients, who are older than 12.5 months or have a pre-op AI of 38.7° or a post-op AI of 26.4°, are also more likely to fail of CR procedure.

Background: Developmental dysplasia of the hip (DDH) is the most common deformity of the lower extremity in children. The biomechanical change during closed reduction (CR) focused on cartilage contact pressure (CCP) has not been studied. Thereby, we try to provide insight into biomechanical factors potentially responsible for the success of CR treatment sand complications by using finite element analysis (FEA) for the first time. Methods: Finite element models of one patient with DDH were established based on the data of MRI scan on which cartilage contact pressure was measured. During CR, CCP between the femoral head and acetabulum in different abduction and flexion angles were tested to estimate the efficacy and potential risk factors of avascular necrosis (AVN) following CR. Results: A 3D reconstruction by the FEA method was performed on a 16 months of age girl with DDH on the right side. The acetabulum of the involved side showed a long, narrow, and “flat-shaped” deformity, whereas the femoral head was smaller and irregular compared with the contralateral side. With increased abduction angle, the stress of the posterior acetabulum increased significantly, and the stress on the lateral part of the femoral head increased as well. The changes of CCP in the superior acetabulum were not apparent during CR. There were no detectable differences in terms of pressure on the femoral head. Conclusions: Severe dislocation (IHDI grade III and IV) in children showed a high mismatch between the femoral head and acetabulum. Increased abduction angle corresponded with high contact pressure, which might relate to AVN, whereas increased flexion angle was not. Enhanced pressure on the lateral part of the femoral head might increase the risk of AVN.

Background It remains controversial whether the older age to perform closed reduction (CR) procedure for developmental dysplasia of the hip (DDH), the higher incidence of complications. The aim of this study is to evaluate the midterm outcome of CR for DDH among difference age groups, and to analyze and identify risk factors for the failure of this procedure. Methods Clinical data of 107 DDH patients, who received CR, were retrospectively reviewed. Data were divided into three groups according to initial treatment age (Group I: younger than 12 months; Group II: 12 months to less or equal to18 months; Group III: older than 18 months). The presence of avascular necrosis (AVN), residual acetabular dysplasia (RAD), re-dislocation, and further surgeries (FS) were observed. The risk factors were identified for those outcomes aforementioned using univariable logistic regression models. For identified risk factor age, pre-op acetabular index (AI) and post-op AI, their prediction of CR failure were evaluated by receiver operating characteristics curve (ROC).Results A total of 107 patients (156 hips) undergoing CR procedure were evaluated with a median age at initial reduction of 13.0±5.4 months (range, 4 to 28 mo). Mean follow-up time in this study was 6.7±0.8 years (range, 3-8 years). The incidence of AVN, RAD and re-dislocation was 15.4% (24/156), 17.3% (27/156) and 14.7% (23/156) respectively. For AVN, RAD and re-dislocation, the significant risk factors are pre-op IHDI IV (p=0.033), age≥18 months (p=0.012), and pre-op IHDI IV (p=0.004) and walking (p=0.011), respectively. The areas under the ROC curve of each type of failures were 0.841 (post-op AI), 0.688 (pre-op AI) and 0.650 (age).Conclusions Severe DDH patients older than 18 months with CR procedure may result in a high risk of RAD complication. Re-dislocation is significantly associated with pre-op IHDI IV and walking. Patients, who are older than 12.5 months or have a pre-op AI of 38.7° or a post-op AI of 26.4°, are also more likely to fail of CR procedure.

Background: Developmental dysplasia of the hip (DDH) is the most common deformity of the lower extremity in children. The biomechanical change during closed reduction (CR) focused on cartilage contact pressure (CCP) has not been studied. Thereby, we try to provide insight into biomechanical factors potentially responsible for the success of CR treatment sand complications by using finite element analysis (FEA) for the first time.Methods: Finite element models of one patient with DDH were established based on the data of MRI scan on which cartilage contact pressure was measured. During CR, CCP between the femoral head and acetabulum in different abduction and flexion angles were tested to estimate the efficacy and potential risk factors of avascular necrosis (AVN) following CR.Results: A 3D reconstruction by the FEA method was performed on a sixteen months of age girl with DDH on the right side. The acetabulum of the involved side showed a long, narrow, and "flat-shaped" deformity, whereas the femoral head was smaller and irregular compared with the contralateral side. With increased abduction angle, the stress of the posterior acetabulum increased significantly, and the stress on the lateral part of the femoral head increased as well. The changes of CCP in the superior acetabulum were not apparent during CR. There were no detectable differences in terms of pressure on the femoral head.Conclusions: Severe dislocation (IHDI grade III and IV) in children showed a high mismatch between the femoral head and acetabulum. Increased abduction angle corresponded with high contact pressure, which might relate to AVN, whereas increased flexion angle was not. Enhanced pressure on the lateral part of the femoral head might increase the risk of AVN.

Background: Congenital talipes equinovarus (clubfoot), one of the most regular pediatric congenital skeletal anomalies, seriously affects the normal growth and development of about 1 in 1000 newborns. Although it has been investigated widely, the etiology and pathogenesis of clubfoot are still controversial. Material/Methods: g: Profiler, NetworkAnalyst and WebGestalt were used to probe the enriched signaling pathways by using the Gene Ontology (GO), Human Phenotype Ontology (HP), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome (REAC), and WikiPathways (WP) databases. Large numbers of enriched signaling pathways were identified using the integrated bioinformatics enrichment analyses. Results: Apoptosis or programmed cell death (PCD), disease, muscle contraction, metabolism, and immune system were the top functions. Embryo or organ morphogenesis and development, cell or muscle contraction, and apoptosis were the top biological processes, and cell/muscle contraction and apoptosis were the top molecular functions using enriched GO terms analysis. There were a large number of complex interactions in the genes, enriched pathways, and transcription factor (TF)-miRNA co-regulatory networks. Transcription factors such as FOXN3, GLI3, HOX, and NCOR2 family regulated the gene expression of APAF1, BCL2, BID, CASP, MTHFR, and TPM family. Conclusions: The results of bioinformatics enrichment analysis not only supported the previously proposed hypotheses, e.g., extracellular matrix (ECM) abnormality, fetal movement reducing, genetic abnormality, muscle abnormality, neurological abnormality, skeletal abnormality and vascular abnormality, but also indicated that cellular or immune responses to external stimulus, molecular transport and metabolism may be new etiological mechanisms in clubfoot.