Case series of congenital pseudarthrosis of the tibia unfulfilling neurofibromatosis type 1 diagnosis: 21% with somatic NF1 haploinsufficiency in the periosteum.

Up to 84% of patients with congenital pseudarthrosis of the tibia (CPT) present with neurofibromatosis type 1 (NF1) (NF1-CPT). However, the etiology of CPT not fulfilling the NIH diagnostic criteria for NF1 (non-NF1-CPT) is not well understood. Here, we collected the periosteum tissue from the pseudarthrosis (PA) site of 43 non-NF1-CPT patients and six patients with NF1-CPT, together with the blood or oral specimen of trios (probands and unaffected parents). Whole-exome plus copy number variation sequencing, multiplex ligation-dependent probe amplification (MLPA), ultra-high amplicon sequencing, and Sanger sequencing were employed to identify pathogenic variants. The result showed that nine tissues of 43 non-NF1-CPT patients (21%) had somatic mono-allelic NF1 inactivation, and five of six NF1-CPT patients (83.3%) had bi-allelic NF1 inactivation in tissues. However, previous literature involving genetic testing did not reveal somatic mosaicism in non-NF1-CPT patients so far. In NF1-CPT patients, when the results from earlier reports and the present study were combined, 66.7% of them showed somatic NF1 inactivation in PA tissues other than germline inactivation. Furthermore, no diagnostic variants from other known genes (GNAS, AKT1, PDGFRB, and NOTCH3) related to skeletal dysplasia were identified in the nine NF1 positive non-NF1-CPT patients and six NF1-CPT patients. In conclusion, we detected evident somatic mono-allelic NF1 inactivation in the non-NF1-CPT. Thus, for pediatric patients without NF1 diagnosis, somatic mutations in NF1 are important.

New insights into pathogenesis of congenital pseudarthrosis of tibia in children using periosteum proteomics analysis.

RATIONALE: The exact etiology and pathogenesis of congenital pseudarthrosis of tibia (CPT) are not clear. Quantitative proteomics analysis plays a vital role in disease pathology research. Tandem mass tag (TMT)-based proteomics techniques were employed to identify and analyze the differentially expressed proteins (DEP) in the tibia periosteum tissues of CPT patients. METHODS: The samples were divided into three groups: CPT with NF1 group, CPT without NF1 group (non-NF1-CPT), and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 were used as the thresholds to screen DEPs. Subsequently, bioinformatics resources such as online tools DAVID and String were used to generate gene ontology (GO) annotation, KEGG pathways enrichment, and protein-protein interaction (PPI) network for these DEPs. RESULTS: The results show that a total of 347 proteins were differentially expressed in NF1-CPT groups, 212 of which were upregulated and 135 were downregulated. There were more DEPs in non-NF1-CPT groups; we identified 467 DEPs, including 281 upregulated and 186 downregulated. Among them, NF1-CPT groups and non-NF1-CPT groups shared 231 DEPs, and the remaining 230 DEPs showed the same expression trend in the two disease groups, with 117 upregulated and 113 downregulated. In particular, 116 proteins were altered only in NF1-CPT groups (94 were upregulated and 22 were downregulated), whereas 236 proteins were altered only in non-NF1-CPT groups (164 were upregulated and 72 were downregulated). Finally, compared with non-NF1-CPT groups, 47 proteins changed 1.5-fold and P-value < 0.05 in NF1-CPT groups. CONCLUSIONS: To sum up, we found that common DEPS in periosteum of NF1-CPT and non-NF1-CPT groups are mainly involved in cell matrix assembly, cell adhesion, AKT-PI3K signal pathway activation, and vascular agglutination, which indicate that these are the pathological characteristics of CPT. The osteogenic ability is weak, the osteoclastic ability is strong, the vascular lumen is narrow, the invasive growth and the proliferation of fibroblasts are enhanced in CPT patients.

The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture.

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non-union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT-PCR, Western blot and immunostaining assays. Finally, we injected lentivirus-NF1 (Lv-NF1) to rat non-union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down-regulated in non-union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non-union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non-union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.

Combination of intramedullary rod, wrapping bone grafting and Ilizarov's fixator for the treatment of Crawford type IV congenital pseudarthrosis of the tibia: mid-term follow up of 56 cases.

BACKGROUND: The purpose of this study was to investigate the initial union rate, refracture rate and residual deformities of congenital pseudarthrosis of the tibia (CPT), using combined surgery including pseudarthrosis resection, intramedullary rodding, autogenous iliac bone grafting and Ilizarov's fixator, with a mean 5.2 years follow-up. METHODS: We retrospectively reviewed the records and diagrams of patients with Crawford type IV congenital pseudarthrosis of the tibia between February 2007 and March 2010. Patients managed by pseudarthrosis resection, intramedullary rod of the tibia, wrapping autogenous iliac bone grafting and Ilizarov's fixator were enrolled. We evaluated the bone union rate, tibial alignment, limb length discrepancy (LLD), valgus deformity of the ankle and the frequencies of refracture during period of follow-up. RESULTS: There were 56 cases enrolled in the study, with a mean follow-up 5.2 years (range, 3 to 6.7 years). The mean age of the patients at surgery was 3.5 years (range, 1.5 to 12.4 years). Fifty (89.2 %) of the 56 patients had primary bone union at site of pseudarthrosis, while 5 obtained union after second surgery and 1 failed. The average time spent to obtain pseudarthrosis initial union was 4.5 months (range, 3.0 to 10.0 months) and mean duration of Ilizarov treatment was 4.7 months (range, 3.2 to 10.4 months). Eleven (19.6 %) patients had proximal tibial valgus with a mean angle of 9.5° (range, 5 to 24°), while 10 (17.9 %) patients had ankle valgus deformities with a mean of 12.3° (range, 6 to 21°). Sixteen (28.6 %) patients had an average 2.2 cm LLD (range, 1.5-4.2 cm). Of the 50 cases who obtained initial bone union of pseudarthrosis, 13 (26.0 %) had refracture which need cast immobilization or secondary surgery. CONCLUSIONS: This combined surgery obtained initial union rate of 89.2 % at primary surgery while the refracture rate is 26.0 %. However, residual deformities such as proximal tibial valgus, LLD and ankle valgus were also existed which should be pay more attention to and dealt with. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov under the name "The Effect of Combined Surgery in Management of Congenital Pseudarthrosis of Tibia" ( NCT02640040 ), which was released on August 31, 2015.

Research on investment optimization and coordination of fresh supply chain considering misreporting behavior under blockchain technology.

In the traditional fresh supply chain, farmers commonly conceal the true quality information of their products in order to achieve better sales. This article focuses on the use of blockchain technology to address the issue of false freshness reporting in a two-level fresh supply chain consisting of a rural cooperative and a supermarket. Taking into account the dual losses of quality and quantity in the process of agricultural products transportation, the impacts of the product freshness and the blockchain investment level on random market demand are quantified in this paper. And game models for centralized and decentralized decision-making before and after investing in blockchain technology are proposed. By comparing the supply chain optimal decisions and performances under different scenarios, a revenue-cost sharing contract is designed to coordinate the decentralized decision-making. Simulation results show that the application of the blockchain technology can further consolidate the superiority of the centralized decision-making. However, there is a certain threshold for the application of the blockchain technology in decentralized decision-making. When the unit cost of blockchain exceeds the threshold, the rural cooperative will abandon its cooperation with the supermarket due to reduced profits. And the combined contract also has a threshold boundary for its coordinating effect on decentralized decision-making.

Research on trust mechanism of supply chain finance under Industrial Internet embedded with blockchain.

In traditional supply chain finance, the financing of enterprise mainly relies on the credit segmentation of the core enterprise, resulting in a short trust transmission radius and poor financing ability. The development of Internet technology, while expanding financing channels, has also seen an increasing severity in issues such as information fraud and data breaches, which has further aggravated the trust crisis in supply chain finance. This paper integrates blockchain technology into the industrial internet platform and analyzes the applicability of both in empowering supply chain financial trust. Then a supply chain financial trust framework, which emphasizes information sharing, data security, and trust circulation, is proposed. Furthermore, combined with the theories of Funk-SVD and entropy value, this paper designs a global trust evaluation mechanism that facilitates the trust circulation in supply chain finance and proposes a recommendation algorithm for global trust. With the testing conducted using the Epinions dataset, it is found that the algorithm proposed in this paper has a strong data dimensionality reduction and concentration ability, especially for large sample data, it can obtain more accurate evaluation values with less space occupation, thus enhancing the trust circulation ability of supply chain finance. Finally, the paper puts forward specific policy recommendations for the implementation of the supply chain finance information mechanism, aiming to better improve the financing accessibility of enterprises in supply chain, particularly small and medium-sized enterprises.

Comparative study of different extendable intramedullary rods combined with surgery in the treatment of congenital pseudarthrosis of the tibia.

BACKGROUND: When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture PURPOSE: To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children METHODS: From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. EXCLUSION CRITERIA: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated RESULTS: It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years CONCLUSION: Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research.

METTL3 promotes the osteogenic differentiation of periosteum-derived MSCs via regulation of the HOXD8/ITGA5 axis in congenital pseudarthrosis.

Background: Congenital pseudarthrosis of the tibia (CPT) is a dominant health challenge in pediatric orthopedics. The essential process in the development of CPT is the limited capacity of mesenchymal stem cells (MSCs) derived from CPT to undergo osteogenic differentiation. Our research aimed to elucidate the role and mechanism of methyltransferase-like 3 (METTL3) in the osteogenic differentiation process of CPT MSCs. Methods: The osteogenic differentiation medium was used to culture MSCs, and the detection of osteogenic differentiation was performed using Alizarin Red S and alkaline phosphatase (ALP) assays. Gene or protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, or immunofluorescence (IF) staining. The m6A modification of Homeobox D8 (HOXD8) was verified by methylated RNA immunoprecipitation (MeRIP) assay. Interactions between METTL3 and HOXD8 or HOXD8 and integrin alpha 5 (ITGA5) promoter were validated by the luciferase reporter gene, RIP, and chromatin immunoprecipitation (ChIP) assays. Results: METTL3 overexpression enhanced CPT MSCs' osteogenic differentiation. METTL3 stabilized the HOXD8 in an m6A-dependent manner. Moreover, the overexpressed ITGA5 up-regulated the CPT MSCs' osteogenic differentiation. Further, HOXD8 could transcriptionally activate ITGA5. METTL3 increased the transcription of ITGA5 via HOXD8 to enhance the osteogenic differentiation of CPT MSCs. Conclusion: METTL3 promoted osteogenic differentiation via modulating the HOXD8/ITGA5 axis in CPT MSCs.

Is physeal distraction osteogenesis a good choice to treat CPT patients with tibial shortening?

The purpose of this study was to evaluate the healing index and complications of distraction osteogenesis through the physis in children with Congenital pseudarthrosis of the tibia (CPT) using Ilizarov external fixation device. Nine children with CPT who underwent distraction osteogenesis through the physis surgery with an Ilizarov external fixation device between June 2018 and August 2020 were included in the study. The average follow-up time was 36.1 months. X-ray examination was performed 1 month after physis lengthening, and the callus quality was evaluated using the Li classification. Any complications and the quality of the callus after tibial lengthening were followed up. The average age at the time of operation was 9.4 years, and the average follow-up time was 36.1 months. The average lengthening length of children with CPT was 6.6 cm. The incidence of good callus morphology was 100%, and the healing index was 51.1 d/cm. The average fixation time of the external fixation device was 316 days. Needle tract infection occurred in one case, ankle stiffness occurred in one case, ankle plantar flexion 20° deformity occurred in one case, angular deformity of the tibial lengthening segment occurred in one case (7°) and limited movement of knee joint occurred in one case (0-20°-70°). The osteogenic quality of the patients of distraction osteogenesis through the physis with tibial shortening and small diameter of the proximal tibia is good, which provides a choice of operation for the children with CPT.

Circ_0000888 regulates osteogenic differentiation of periosteal mesenchymal stem cells in congenital pseudarthrosis of the tibia.

Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.

Clinical study of a new type of telescopic rod for the treatment of congenital pseudarthrosis of the tibia in children.

The purpose of this study was to investigate the initial efficacy of a new telescopic rod in the treatment of congenital pseudarthrosis of tibia (CPT) in children. A new type of telescopic rod for children was designed and its clinical results were evaluated. There were nine cases of CPT on the right and six cases on the left; there were six females and nine males. The average age at operation was 35.5 months. There were 12 cases with neurofibromatosis type 1 and 4 cases with proximal tibial dysplasia. The initial healing of tibial pseudarthrosis, proximal tibial valgus deformity, tibial length, ankle valgus, ankle function, and intramedullary rod displacement were evaluated during follow-up. All 15 cases were followed up for an average of 18.2 months, 14 cases achieved initial healing, with an average healing time of 4.3 months. Ten cases had unequal lengths of the tibia, with an average of 0.9 cm. Proximal tibial valgus occurred in seven cases and ankle valgus occurred in one child. The average range of motion of the ankle joint was 23° and the average plantar flexion was 42°. The average extension of the new telescopic rod was 1.6 cm. The displacement of the telescopic rod occurred in seven cases, there was no epiphyseal plate tethering and re-fracture. The new children's telescopic rod has a reasonable design and can extend with the growth of tibia. There are no complications of epiphyseal plate tethering and re-fracture. It provides a new choice of intramedullary fixation for the treatment of CPT.

Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?

Background: Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT. Methods: A total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements. Results: 74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (-0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification. Conclusions: We found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.

Analysis of risk factors affecting union and refracture after combined surgery for congenital pseudarthrosis of the tibia: a retrospective study of 255 cases.

BACKGROUND: Congenital pseudarthrosis of the tibia (CPT) is a rare disease occurring in children. The aim of this study is to identify the factors affecting bone union and re-fracture after surgery for CPT and to provide reliable evidence for clinics. METHODS: We collected the detailed information of 255 cases with Crawford IV CPT treated by combined surgery in our hospital from 2013 to 2020. Basic characteristics were recorded. Univariate variance and logistic regression analysis were used to compare the correlations between factors and outcomes. RESULTS: 92.5% of patients achieved primary union, 7.5% of patients had non-union and 13.3% of patients had re-fracture. Logistic regression analysis showed that age at index surgery (Coef. = 0.171, 95%CI 0.015-0.327, P = 0.032), and CPT location (Coef. = - 1.337, 95%CI - 2.218-0.456, P = 0.003) had statistical differences, while no factors had significant correlation with re-fracture. Furthermore, ROC curve showed that the optimal age threshold for first surgery was 2.37 years old. CONCLUSIONS: For patients with Crawford IV CPT treated by combined surgery, the younger the age at index surgery and the closer the CPT location to the distal end, the easier to achieve bone union.

Retrospective Case Analysis of 104 Cases of Talipes Equinus.

A retrospective study of 104 patients (81 male and 23 females, the age range from 2 to 288days) with talipes equinus was conducted to explore the case factors associated with it. We analyzed and discussed the correlation of plaster correction times, age of first visit, gender, and birthplace of patients in the department and understood their correlation and causality. The data were analyzed using frequency analysis, normality test, chi-square goodness-of-fit test, chi-square test, and PLS regression. The findings are set out below. All the distributions of the number of plaster casts in the samples did not have normality. Therefore, we used the nonparametric test and partial least squares regression (PLS regression) and found that the number of plaster casts was more closely related to the age at first visit, gender, and birthplace and had a strong positive correlation. There was a negative correlation between the times of plaster correction and the compliance of braces. The lower the compliance of patients with braces, the more times the plaster correction will be conducted.

miR-30a inhibits the osteogenic differentiation of the tibia-derived MSCs in congenital pseudarthrosis via targeting HOXD8.

Background: Congenital pseudarthrosis of the tibia (CPT) is an uncommon congenital deformity and a special subtype of bone nonunion. The lower ability of osteogenic differentiation in CPT-derived mesenchymal stem cells (MSCs) could result in progression of CPT, and miR-30a could inhibit osteogenic differentiation. However, the role of miR-30a in CPT-derived MSCs remains unclear. Methods: The osteogenic differentiation of CPT-derived MSCs treated with the miR-30a inhibitor was tested by Alizarin Red S staining and alkaline phosphatase (ALP) activity. The expression levels of protein and mRNA were assessed by Western blot or quantitative reverse transcription-polymerase chain reaction (RT-qPCR), respectively. The interplay between miR-30a and HOXD8 was investigated by a dual-luciferase reporter assay. Chromatin immunoprecipitation (ChIP) was conducted to assess the binding relationship between HOXD8 and RUNX2 promoter. Results: CPT-derived MSCs showed a lower ability of osteogenic differentiation than normal MSCs. miR-30a increased in CPT-derived MSCs, and miR-30a downregulation promoted the osteogenic differentiation of CPT-derived MSCs. Meanwhile, HOXD8 is a direct target for miR-30a, and HOXD8 could transcriptionally activate RUNX2. In addition, miR-30a could inhibit the osteogenic differentiation of CPT-derived MSCs by negatively regulating HOXD8. Conclusion: miR-30a inhibits the osteogenic differentiation of CPT-derived MSCs by targeting HOXD8. Thus, this study might supply a novel strategy against CPT.

Epidemiological and clinical characteristics of congenital pseudarthrosis of the tibia in China.

Background: Congenital pseudarthrosis of the tibia (CPT) is a refractory and rare disease. Because of its extremely low incidence, little is known about its clinical features. In this retrospective study, we aim to analyze the clinical characteristics of patients with CPT. Materials and methods: This is a retrospective study of children with CPT identified by the radiological review. Investigations of CPT included general conditions, the characteristics of CPT, treatment methods, and surgical complications. Results: We collected 514 CPT cases from March 1999 to March 2020 in our hospital, such as 317 (61.67%) boys, 197 (38.33%) girls; 330 (62.86%) in Crawford IV; 510 (97.14%) in mid and distal 1/3 tibia; 481 (93.58%) in less than 3 years at onset age; 297 (57.78%) in less than 3 years at the first outpatient visit. The most common post-operative complication was ankle valgus (101, 39.60%), followed by limb length discrepancy (91, 35.69%), refracture (38, 14.90%), osteomyelitis (15, 5.88%), and removal of internal fixation (10, 3.93%). Conclusions: CPT with a higher incidence of Crawford IV frequently occurs in boys and the middle or distal part of the tibia; most patients have the onset age and first outpatient visit before 3 years; the major surgical complications are ankle valgus and limb length discrepancy.

Evaluation of the efficacy of ipsilateral fibular transfer for reconstruction of large tibial defects in children: a retrospective study.

BACKGROUND: Reconstruction of large tibial defects is often a major challenge in limb salvage. This study aimed to evaluate initial follow-up results of ipsilateral fibula transfer for the treatment of large tibial defects in children. METHODS: A retrospective study was performed between September 2014 and April 2021. Ten children were identified as having large tibial defects. The children underwent ipsilateral fibula transfer. We then evaluated initial healing, tibial length discrepancy, ankle varus/valgus, fibular position, refracture, infection, and function. RESULTS: Five boys and five girls, with an average age of 7.2 years, were evaluated. The transferred fibula was united in the patients. The mean follow-up period after fibular transposition was 43 months. The patients achieved primary bone union; the mean time to union was 8.4 months (range, 4-18 months). Complications included refracture (30%), infection (40%), tibia malunion (30%), ankle varus (30%), sensory loss of toes (10%), and ankle valgus (10%). No other major complications were observed. All 10 patients were able to perform activities of daily living and return to their normal activities. CONCLUSION: Ipsilateral fibula transfer is a salvage surgery for the treatment of large tibial defects in children with congenital pseudoarthrosis of the tibia, traumatic nonunion of the tibia, and/or tibial defect after chronic osteomyelitis. However, long-term results still need to be followed up.

Research on evaluation of manufacturing cloud service oriented to environmental benefits of supply chain.

From the perspective of improving the environmental benefits of the supply chain, in this paper, the evaluation index system of manufacturing cloud service is established. It is oriented to the environmental benefits of the supply chain and takes into account the environmental indicators of the candidate providers. The fuzzy DEMATEL modified entropy method is used to calculate the comprehensive weight of the evaluation index. Then, the candidate manufacturing cloud service providers are selected based on gray relational analysis to ensure the rationality of the evaluation results. The evaluation system not only objectively considers the situation of each supplier but also reflects the platform's emphasis on low-carbon environmental factors. Finally, this paper takes the seat suppliers' selection problem in the supply chain of Tianjin industrial cloud automotive mold supply chain as examples to verify the practical significance of this model. At the same time, this paper can provide ideas for the application of cloud manufacturing mode and the solution of supply chain environment problems.

Application of the "telescopic rod" in a combined surgical technique for the treatment of congenital pseudarthrosis of the tibia in children.

BACKGROUND: The current surgical treatment of choice is the combination surgical technique, involving tibial intramedullary fixation to maintain the mechanical axis and mechanical stability of tibial pseudarthrosis. In traditional combined surgery, the Williams rod is often used. Long-term intramedullary fixation of the foot and ankle will affect the ankle joint function of children. The intramedullary rod is relatively shorter due to the growth of the distal tibia. In addition, there are some complications such as epiphyseal bone bridge and high-arched foot. The use of a telescopic intramedullary rod may avoid these complications. PURPOSES: To investigate the initial effect of the "telescopic rod" in a combined surgical technique for the treatment of congenital pseudarthrosis of the tibia in children. METHODS: A retrospective study including 15 patients with Crawford type IV CPT who were treated using a combined surgical technique and the telescopic rod from January 2017 to May 2018. The average age at the time of surgery was 43.3 months (16-126 months). Of the 15 patients, 7 had proximal tibia dysplasia and 12 exhibited neurofibromatosis type 1. The combined surgical technique using the telescopic rod included the excision of pseudarthrosis, intramedullary rod insertion, installation of Ilizarov's fixator, tibia-fibular cross union, and wrapping autogenic iliac bone graft. The incidence of refracture, ankle valgus, tibial valgus, and limb length discrepancy (LLD) in patients were investigated. RESULTS: All patients achieved primary union with an average follow-up time of 37.3 months (26-42 months). The mean primary union time was 4.5 months (4.0-5.6 months). Nine cases showed LLD (60%), with an average limb length of 1.1 cm (0.5-2.0 cm). Ankle valgus, proximal tibial valgus, telescopic rod displacement, and epiphyseal plate tethering occurred in 1 case (6.6%) (18°), 3 cases (20%) (10°, 5°, and 6°, respectively), 6 cases (40%), and 2 cases (13%), respectively. There were no refractures during the follow-up periods. CONCLUSION: Although there are complications such as intramedullary rod displacement while using the telescopic rod in a combined surgery, the primary healing rate of congenital pseudarthrosis of the tibia in children is high.

Serum-derived exosomes from neurofibromatosis type 1 congenital tibial pseudarthrosis impaired bone by promoting osteoclastogenesis and inhibiting osteogenesis.

Treatment of congenital pseudarthrosis of the tibia (CPT) still is full of challenges in pediatric orthopedist. Serum-derived exosomes (SDEs) have been proven to be participated in bone remodeling. However, the molecular changes in SDEs of CPT children and their pathologies have not been elucidated. In this study, SDEs were isolated and purified from CPT patients (CPT-SDEs) associated with neurofibromatosis type 1 (NF1) and normal children (Norm-SDEs). Then we obtained the proteomics profile of SDEs by combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag label-based quantitation. In vitro, the efficacy of SDEs on osteoblastic differentiation of MC3T3-E1 cells and osteoclastogenesis ability of RAW264.7 cells were evaluated by quantitative real-time PCR (qRT-PCR) and cytochemical staining. In vivo, we used micro-CT to assess cortical bone mass and trabecular microstructures to reflect the influence of SDEs on bone remodeling after injection into the tail vein of rats. Based on proteomics analysis, 410 differentially expressed proteins, including 289 downregulated proteins and 121 upregulated proteins, were identified in the CPT-SDEs. These proteins have multiple biological functions associated with cellular metabolic processes, catalytic activity, and protein binding, which are important for cell differentiation and proliferation. In vitro, CPT-SDEs decreased the osteogenic differentiation of MC3T3-E1 cells and promoted the osteoclastogenesis of RAW264.7 cells. Injection of CPT-SDEs into the tail vein for two months resulted in bone loss in rats, as indicated by the decrease in trabecular and cortical bone mass. Our findings demonstrated the differences in proteins in SDEs between normal and CPT children with NF1. These differentially expressed proteins in CPT-SDEs contributed to deteriorating trabecular bone microstructures by inhibiting bone formation and stimulating bone resorption.