The most stable pinning configurations in transverse supracondylar humerus fracture fixation in children: A novel three-dimensional finite element analysis of a pediatric bone model.

PURPOSE: This study aimed at finding out the effect of exit height, trajectory and number of pins on the stability of cross and divergent-lateral pins used in the fixation of extension-type, transverse supracondylar humerus fracture (SHF) in children, based on finite element analysis. METHODS: Distal humerus model consisting of the ossific nucleus of the capitellum (ONC) and distal cartilage of a 6-year-old boy was developed via three-dimensional finite modeling. Various cross and divergent-lateral pinning models with either two or three pins were simulated on an extension-type, transverse SHF and tested in six loading directions. RESULTS: Two-cross pins and 2-divergent-lateral pins were more stable against torsional and translation forces respectively, while 3-cross pins were the most stable against all forces. The cross pins exiting at the upper border of the distal metaphyseal-diaphyseal junction (MDJ) had the best stiffness among the 2-cross pins, while the lateral pins with a middle third ONC distal pin provided the best stiffness among the 2-lateral pins. A third olecranon fossa pin greatly enhanced stability of the 2-lateral pins. CONCLUSION: For typical transverse fractures, 2-cross pins are found to be superior to 2-divergent lateral pins only against torsional forces. Pins exiting at the upper border of the MDJ provides the best mechanical stability with 2-cross pins. Two-divergent-lateral pins with a distal pin going through the middle third of the ONC provides the best mechanical stability against translation forces for these transverse fractures. Three-cross pins however offer the best mechanical stability against both translation and torsional forces. This study offers important clues in the preoperative evaluation and management of extension-type supracondylar fractures in children.

[Three-dimensional finite element analysis of Kirschner wire fixation configuration for supracondylar fracture of humerus fracture in children].

OBJECTIVE: To establish a new mechanical model of distal humerus in children with epiphysial cartilage, stimulate supracondylar humerus fracture and perform three dimensional finite elements, and study effect of pins numbers, pin tract, outlet height and pin configurations on stability of fixation. METHODS: Three dimensional computed tomography (CT) data of 6-year-old boy with distal humerus was downloaded from picture archiving and communications systems software (PACS), the data of picture was imported into Simpleware and SolidWorks 2016 software to establish distal humerus fracture in children contained ossific nucleus of the capitellum (ONC) and distal cartilage. Normal extense supracondylar humerus fracture model was established to stimulate configurations of crossed and lateral pinning fixation, 30 N was added on the direction of flexion extension and varus valgus, while 50 N was added on the direction of internal and external turning. Stability was analyzed by displacement degree of distal fracture. RESULTS: Among 2-pin configurations, 2-crossed pins were more stable against rotation forces which could resist rotation stress over 2 585 Nmm/ °, while low position through ONC of 2-divergent lateral pins were more stable, which could resist stress of 45 N /mm and 190 N /mm during the test of resistant strains and varus-valgus stress. The third pins was added into the more stable lateral 2-pins, the stability in all directions were increased obviously, and 3 crossed pins is the most stable, stress of flexion-extension, varus-valgus and internal-external turning were 198 N /mm, 395 N /mm and 6 251 Nmm/ °. CONCLUSION: Two-divergent lateral pins could provide enough stability for supracondylar humerus fracture in children. In two-crossed pins, the upper border of MDJ could provide the best stability. Three-crossed pins could offer the best stability against both translation and rotation forces.

WISP-2, an upregulated gene in hip cartilage from the DDH model rats, induces chondrocyte apoptosis through PPARγ in vitro.

Chondrocyte apoptosis plays an important role in the developmental dysplasia of the hip (DDH) development. It has been found that WNT1 inducible signaling pathway protein 2 (WISP-2) and peroxisome proliferator-activated receptor γ (PPARγ) are involved in cell apoptosis. In this study, we performed the straight-leg swaddling DDH rat model and we found that cartilage degradation and chondrocyte apoptosis were remarkably increased in DDH rats in vivo. Moreover, we found that WISP-2 was upregulated in hip acetabular cartilage of DDH rats compared to control rats. Next, the effects of WISP-2 on chondrocyte apoptosis and its possible underlying mechanism were examined in vitro. The lentivirus-mediated gain- and loss-of-function experiments of WISP-2 and peroxisome proliferator-activated receptor γ (PPARγ) for cell viability and apoptosis were performed in primary rat chondrocytes. The results showed that the overexpression of WISP-2 induced chondrocyte apoptosis, and knockdown of WISP-2 could suppress the chondrocyte apoptosis induced by advanced glycation end products (AGE). Additionally, WISP-2 could negatively regulate the expression of PPARγ in chondrocytes. Moreover, the knockdown of PPARγ promoted chondrocyte apoptosis and overexpression of PPARγ abated the increased apoptosis and decreased cell viability of chondrocytes induced by WISP-2. This study demonstrated that WISP-2 might contribute to chondrocyte apoptosis of hip acetabular cartilage through regulating PPARγ expression and activation, which may play an important role in the development of DDH.

Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression.

Strategies targeted vascular endothelial growth factor (VEGF)-dependent osteosarcoma progression are limited although important progress has been made in illustrating the mechanisms. Here we identified circ_001621 as one of the significantly upregulated circular RNAs (circRNAs) by circRNAs microarrays. We found that patients with high circ_001621 expression had a shorter survival time. Moreover, we found several potential sponge micro RNAs (miRNA) of circ_001621 with Circular RNA Interactome database. Among the candidate sponge, we elucidated the association of circ_001621 and miR-578. In addition, we demonstrated that miR-578 targeted circ_001621 directly. Functionally, we set up the experimental system to investigate the effects of circ_001621/miR-578/VEGF interaction in vitro and in vivo. Results indicated circ_001621-promoted osteosarcoma proliferation and migration via attenuating the inhibition of cyclin-dependent kinase 4 (CDK4) and matrix metallopeptidase 9 (MMP9) by miR-578, respectively. Nude mice experiment was further performed to estimate the promotion of metastasis by circ_001621. The present study evaluated the mechanisms underlying circ_001621 enhanced osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.

A two-stage retrospective analysis to determine the effect of entry point on higher exit of proximal pins in lateral pinning of supracondylar humerus fracture in children.

BACKGROUND: Kirschner wire fixation remains to be the mainstream treatment modality in unstable or displaced supracondylar humerus fracture in children, with divergent lateral pins being the most preferred due to their sufficient stability and decreased risk of ulnar nerve injury. However, the entry point at which the proximal lateral pin can be inserted to achieve a more proximal exit and maximum divergence has not been reported. This study retrospectively analyzed the characteristics and factors influencing the entry and exit points of the proximal lateral pins. METHODS: The study was divided into two stages. In stage one, the entry and exit points of the proximal pins of lateral pinning configuration were analyzed from intra-operative radiographs of children treated for extension-type supracondylar humerus fractures. The coronal and sagittal pin angles formed by the proximal pins were also measured. Using the findings of stage one, we intentionally tried to achieve a more proximal exit with the proximal pins in stage two. Comparisons between groups of patients treated by random and intentional pinnings were done statistically. RESULTS: In the first stage, 47 (29.2%) of the 161 proximal pins exited above the metaphyseal-diaphyseal junction (MDJ) region. Of these, 85.1% entered from lateral and posterior to the ossific nucleus of the capitellum (ONC). The pin angles averaged 58.4° and 90.5° in the coronal and sagittal planes respectively. In the second stage, 47 (65.3%) proximal pins in the intended group exited above the MDJ region, while only 32 (36%) in the random group exited above the MDJ region. CONCLUSION: While aiming at the upper border of the distal MDJ during pinning, lateral pins can easily achieve a higher, proximal exit above the MDJ if inserted from lateral and posterior to the ONC and parallel to the humeral shaft in the sagittal plane. Higher exit can also be easily achieved in younger patients and patients fixated with smaller diameter pins.

Deep hypothermic preservation of autologous skin in the treatment of large-area circumferential multi-plane degloving trauma: a pilot study of 2 cases.

To evaluate the clinical outcome of deep hypothermic preservation of autologous skin in the treatment of large-area skin avulsion. Medium or full thickness-skin slices were harvested from large avulsion flaps between July and November 2017. They were stored in liquid nitrogen by vitrification. After the patient's condition became stable and the growth of the wound granulation tissue was satisfactory, the frozen skin slices were reheated quickly and replanted to the wound. Autologous skin that had been kept by deep cryopreservation had a high survival rate when grafted. It did not create new trauma or bring additional pain to patients. Yet it could shorten the course of treatment and reduce the medical cost for patients. It is an effective and economical way to treat large-area skin avulsion.

A comparative biomechanical study on different fixation techniques in the management of transverse metaphyseal-diaphyseal junction fractures of the distal humerus in children.

BACKGROUND: Metaphyseal-diaphyseal junction (MDJ) fractures of the distal humerus are problematic to reduce and more susceptible to post-operative complications. This biomechanical study was designed to compare Kirschner wires (KW), lateral external fixation, and elastic stable intramedullary nails (ESIN) in simulated transverse MDJ fractures of various heights. METHOD: Sagittally oblique, transverse MDJ fractures were created in fourth-generation composite bone models at three levels: high, mid, and low fractures, respectively, and then fixed with either Kirschner wires, lateral external fixation (EF), or ESIN respectively and tested in extension, flexion, valgus, varus, internal, and external rotations. RESULTS: In the high fractures, ESIN had better overall stiffness than the other techniques. In the mid groups, three crossed pinning (1-medial and 2-lateral pins) had the best overall stiffness, followed by two crossed pinning (1-medial and 1-lateral pins). In the low fractures, three crossed pinning was superior to all other techniques. Two crossed pinning and three -lateral pinning techniques yielded comparable stiffness in the low fracture model. CONCLUSIONS: From a biomechanical perspective, ESIN provides the best overall stability for fractures located in the upper region of the MDJ, while percutaneous pinning is superior in stabilizing fractures of the lower region. Two lateral and one medial pins make the most stable crossed pinning construct for these fractures.

MicroRNA-140 suppresses osteosarcoma tumor growth by enhancing anti-tumor immune response and blocking mTOR signaling.

Immune checkpoint blockade is proved to be a promising therapeutic strategy against several human malignancies. MicroRNAs (miRNAs) are ∼22 nucleotide RNAs that play important roles in regulating gene expression, either suppressing its translation or speeding up its degradation. In this study, we demonstrated that miR-140 acts as a critical modulator of PD-L1 and is significantly reduced in osteosarcoma (OS). MiR-140 was inversely correlated with PD-L1 and luciferase reporter assay confirmed that miR-140 can direct regulate PD-L1 expression by binding to its 3'UTR. MiR-140 failed to influence tumor growth in nude mice, whereas markedly inhibited tumor growth in the immune-competent C57BL/6J mice. Mechanistically, the tumor-suppressive role of miR-140 was associated with the increased infiltrates of cytotoxic CD8+ T cells and the decreased infiltrates of myeloid-derived suppressive cells and regulatory T cells. Moreover, miR-140 significantly inhibited mTOR signaling and combined miR-140 overexpression with pharmacological inhibition of mTOR signaling showed remarkable synergistic anti-tumor effect. Collectively, our findings indicate that miR-140 exerts anti-OS efficacy by targeting immune checkpoint molecule PD-L1 and can be developed as a novel immunotherapeutic agent for the treatment of OS.

Identification and function analysis of contrary genes in Dupuytren's contracture.

The present study aimed to analyze the expression of genes involved in Dupuytren's contracture (DC), using bioinformatic methods. The profile of GSE21221 was downloaded from the gene expression ominibus, which included six samples, derived from fibroblasts and six healthy control samples, derived from carpal-tunnel fibroblasts. A Distributed Intrusion Detection System was used in order to identify differentially expressed genes. The term contrary genes is proposed. Contrary genes were the genes that exhibited opposite expression patterns in the positive and negative groups, and likely exhibited opposite functions. These were identified using Coexpress software. Gene ontology (GO) function analysis was conducted for the contrary genes. A network of GO terms was constructed using the reduce and visualize gene ontology database. Significantly expressed genes (801) and contrary genes (98) were screened. A significant association was observed between Chitinase-3-like protein 1 and ten genes in the positive gene set. Positive regulation of transcription and the activation of nuclear factor-κB (NF-κB)-inducing kinase activity exhibited the highest degree values in the network of GO terms. In the present study, the expression of genes involved in the development of DC was analyzed, and the concept of contrary genes proposed. The genes identified in the present study are involved in the positive regulation of transcription and activation of NF-κB-inducing kinase activity. The contrary genes and GO terms identified in the present study may potentially be used for DC diagnosis and treatment.

CXCL13 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting miR-23a Expression.

CXC chemokines are essential for osteogenic differentiation of bone mesenchymal stem cells (BMSCs) for use in bone tissue engineering and regenerative medicine in clinical settings. However, an accurate understanding of the underlying mechanisms is still needed. In this study, we analyzed the effects of CXC chemokine ligand-13 (CXCL13) on osteogenic differentiation of rat BMSCs and initiated a preliminary discussion on possible mechanisms. BMSCs were isolated from bone marrow of rat and incubated with CXCL13 recombinant protein in differentiation medium. The main osteogenesis indexes were alkaline phosphatase (ALP) activity and calcium nodes. Expression of Runx2 and CXCR5 was determined using western blot, while miRNAs were determined with quantitative-RT-PCR. Si-CXCR5 was transfected into MSCs to silence CXCR5. A miRNA-23a mimic was transfected into BMSCs for overexpression of miRNA-23a. Recombinant CXCL13 induced ALP activity, deposition of calcium salts, and formation of calcium nodes, and it also increased expression of Runx2. The expression of recombinant CXCL13 suppressed expression of miRNA-23a. Overexpression of miR-23a reversed CXCL13 induced-osteogenic differentiation of BMSCs and expression of Runx2. Recombinant CXCL13 attenuated the interaction of miRNA-23a with the Runx2 3'UTR. Silencing of CXCR5 abrogated recombinant CXCL13-induced downregulation of miRNA-23a expression. In summary, CXCL13 promotes osteogenic differentiation of BMSCs by inhibiting miR-23a expression.

CXCL13 promotes the effect of bone marrow mesenchymal stem cells (MSCs) on tendon-bone healing in rats and in C3HIOT1/2 cells.

OBJECTIVES: Mesenchymal stem cells (MSCs) are potential effective therapy for tissue repair and bone regeneration. In present study, the effects of CXC chemokine ligand-13 (CXCL13) were evaluated on tendon-bone healing of rats. METHODS: Tendon bone healing of the rat model was established and biomechanical testing was performed at 2, 4, 8 weeks after surgery. Murine mesenchymal cell line (C3HIOT1/2 cells) was cultured. The expression of miRNA-23a was detected by real-time PCR. The protein expression of ERK1/2, JNK and p38 was detected by western blotting. MiR-23a mimic and inhibitor were used to overexpress or silence the expression of miR-23a. RESULTS: MSCs significantly elevated the levels of ultimate load to failure, stiffness and stress in specimens of rats, the effects of which were enhanced by CXCL13. The expression of miR-23a was down-regulated and the protein of ERK1/2 level was up-regulated by CXCL13 treatment in both in vivo and in vitro experiments. ERK1/2 expression was elevated by overexpression of miR-23a and reduced by miR-23a inhibitor. CONCLUSIONS: These findings revealed that CXCL13 promoted the tendon-bone healing in rats with MSCs treatment, and implied that the activation of ERK1/2 via miR-23a was involved in the process of MSCs treated bone regeneration.

The neuroprotective mechanism of puerarin in the treatment of acute spinal ischemia-reperfusion injury is linked to cyclin-dependent kinase 5.

Puerarin is shown to exert a variety of pharmacological effects including neuroprotective properties. However, mechanisms of the action are not fully understood. This study was designed to explore the mechanism of puerarin in treatment of acute spinal ischemia-reperfusion injury in rats. Acute spinal ischemia-reperfusion injury was conducted by aortic occlusion in twenty-eight male Sprague-Dawley rats, weighting 230-250 g. The animals were randomly divided into four groups. In the animals with puerarin treatment, 50 mg/kg of puerarin was injected intraperitoneally after reperfusion, and followed by the same dose of injection every 24h for 2 days. In the animals with roscovitine pre-treatment, 30 mg/kg roscovitine was intravenously administrated 60 min before spinal ischemia started. After spinal ischemia for 60 min followed by 48 h of reperfusion, the motor function, spinal infarction volume, apoptosis indices and the activities of Cdk5 and p25 were examined. Acute spinal ischemia-reperfusion resulted in an injury of the spines associated with motor deficit, elevation of Cdk5 and p25 activities, and increase in the spinal apoptosis number and spinal infarction volume. Puerarin improved motor function associated with the decreased apoptosis number, spinal infarction volume, and Cdk5 and p25 activities. The present study indicated that reduction of spinal injury was associated with inhibition of Cdk5 and p25, and that inhibition of Cdk5 and p25 was one of the neuroprotective mechanisms in the puerarin treatment of acute ischemia/reperfusion-induced spinal injury in rats.

The neuroprotective mechanism of puerarin treatment of acute spinal cord injury in rats.

Puerarin extracted from radix puraeriae is shown to exert a variety of pharmacological effects including neuroprotective properties. However, its mechanisms of action are needed to further explore. The study was designed to investigate the mechanism of puerarin treatment of acute spinal cord ischemia-reperfusion injury (SCI/RI) in rats. SCI/RI was conducted in male Sprague-Dawley rats, and 50mg/kg of puerarin was injected intraperitoneally at 1, 2, 4 and 6h after reperfusion, followed by the same dose of injection every 24h for 2 days. Glutamate level, metabotropic glutamate receptors (mGluR) mRNA expression, and apoptosis indices were examined. Neurologic function was assessed at 48 h of reperfusion. SCI/RI caused extensive motor deficit associated with an elevation of glutamate level and mGluRs-1 mRNA expression, while puerarin administration improved motor deficit, and decreased glutamate level and inhibited mGluRs-1 mRNA expression. The present study demonstrated that administration of puerarin reduced the spinal ischemia/reperfusion injury, and suggested that the neuroprotective mechanism of puerarin involved a decrease in glutamate release and mGluRs-1 mRNA expression.

The optimal therapeutic timing and mechanism of puerarin treatment of spinal cord ischemia-reperfusion injury in rats.

AIM OF THE STUDY: The purpose of this study was to explore the optimal therapeutic timing and mechanism of puerarin treatment of spinal cord ischemia-reperfusion injury. MATERIALS AND METHODS: The spinal ischemia-reperfusion injury was conducted in male Sprague-Dawley rats, and 50mg/kg of puerarin was injected intraperitoneally at 1, 2, 4 and 6h after the injury. Motor function was measured 48 h after reperfusion started. Thioredoxin expression and apoptosis indices were determined. RESULTS: Improvement of motor function at 1, 2, and 4h was demonstrated in the animals with puerarin treatment. Ischemia-reperfusion injury resulted in a decrease in the expression of thioredoxin, while puerarin administration elevated the expression of thioredoxin-1/thioredoxin-2 mRNA. Apoptosis indices were significantly reduced by puerarin administration. CONCLUSIONS: We conclude that administration of puerarin within 4h of spinal ischemia-reperfusion injury reduces ischemic reperfusion damage, and that the neuroprotective effect of puerarin involves an increase in the transcription of thioredoxin and a reduction of apoptosis.

Plastic repair for a case with synpolydactyly.

On March 23, 2010, we successfully treated a boy with synpolydactyly who had a total of 31 fingers and toes. Although there was bone syndactyly both the hands of the boy, one-step correction of four extremities was successful, this operation lasted 5 h and 20 min and intraoperative bleeding was about 50 ml. Skin grafting was successful after operation and all incisions healed well. The appearance and function of hands and feet were satisfactory.

[Experimental study on losartan decreasing denervated skeletal muscle atrophy through reducing cell apoptosis].

OBJECTIVE: To explore the role of cell apoptosis in denervated skeletal muscle atrophy in rats and the effect of losartan on it. METHODS: Forty-two Sprague Dawley rats were randomly divided into 3 groups: group I (n = 14, normal control group), group II (n = 14, denervated group) and group III (n = 14, losartan group). The rats were not treated in group I, and were made denervated gastrocnemius models in groups II and III. In group III, the rats were treated with losartan 10 mg/kg x d by gavage and with normal saline in groups I and II. After 4 weeks, gastrocnemius mass to body mass ratio (GAS/BM) served as the degree of muscle atrophy. Apoptotic cells in gastrocnemius were stained in situ by using TUNEL. Gastrocnemius Bcl-2 and Bax protein were quantified by immunohistochemistry and Western blot. Bax/Bcl-2 served as the degree of apoptosis. RESULTS: The ratio of apoptosis was higher in group II than that in group I (11.32% +/- 4.51% vs 0.56% +/- 0.21%, P < 0.05). The ratio of apoptosis was lower in group III than that in group II (7.21% +/- 2.05% vs 11.32% +/- 4.51%, P < 0.05). The atrophy of skeletal muscle (GAS/BM) in group II was more serious than that in group I (11.68 +/- 1.98 vs 12.86 +/- 0.74, P < 0.05), there was no significant difference between group III and group II (12.11 +/- 0.65 vs 11.68 +/- 1.98, P > 0.05). The expression of Bcl-2 in group II (18.3% +/- 4.9%) was significantly lower than that in group I (27.5% +/- 2.8%) and group III (25.5% +/- 3.5%); there was no significant difference between group III and group I (P > 0.05). The expression of Bax in group II (24.1% +/- 3.1%) was significantly higher than that in group I (22.1% +/- 3.6%) and group III (21.7% +/- 2.3%); there was no significant difference between group III and group I (P > 0.05). Western blot results showed that: the expressions of Bcl-2 were 122.5 +/- 14.6 in group II, 135.3 +/- 6.2 in group I and 139.2 +/- 16.2 in group III; showing significant differences between group II and group I, between group III and group II (P < 0.05). The expressions of Bax were 107.1 +/- 15.8 in group II, 89.3 +/- 8.4 in group I, and 94.2 +/- 9.5 in group III; showing significant differences between group II and group I, between group III and group II (P < 0.05). There was no significant difference in the expression of Bcl-2 and Bax between group III and group I (P > 0.05). CONCLUSION: Cell apoptosis plays an important role in denervated skeletal muscle atrophy in rats and may be one of the factors causing skeletal muscle atrophy. Losartan can decrease skeletal muscle cell apoptosis through regulating the ratio of Bax/Bcl-2.

Replantation of completely amputated thumbs with venous arterialization.

PURPOSE: To report a new method of replanting completely amputated thumbs with venous arterialization. METHODS: In 6 replantation surgeries of completely amputated thumbs performed during the period 1999-2003, the proximal artery was anastomosed with a vein of the amputated part to establish inflow and the proximal vein was anastomosed with several other veins in the amputated part to establish outflow. This was because the proper palmar digital arteries were seriously injured or anastomosis of proper palmar digital arteries failed many times. RESULTS: All the replanted thumbs survived, regained good sensory and motor functions, and showed no difference from thumbs replanted conventionally. CONCLUSIONS: Venous arterialization may salvage otherwise unreplantable thumbs.