Customized treatment protocols for patients with closed fracture in hospitals at varying coronavirus disease 2019 (COVID-19) risk.

BACKGROUND: To determine an optimized treatment protocol during the COVID-19 epidemic for patients with closed fracture and delayed surgery. METHODS: The epidemic data of three hospitals, randomly selected from different administrative regions of Wuhan, were analyzed retrospectively from 23 January to 31 March 2020. Changes in the number of confirmed cases per day (cumulative and new) of each region were tracked as a reflection of changing epidemic risk levels. The risk level map was drawn. The epidemic status, treatment protocols, and treatment efficiencies for patients with closed fracture in the three hospitals were compared. RESULTS: Overall, 138 patients with closed fracture were admitted. Each hospital had established its own protocol, according to the initial perceived risk. Based on the risk level map, over the study period, the risk levels of the three regions changed independently and were not in sync. All patients recovered and were timely discharged. No staff member was detected with COVID-19. CONCLUSIONS: The COVID-19 risk level of each area is dynamic. To optimize medical resources, avoid cross-infection, and improve efficiency, changes in epidemic risk should be monitored. For patients with closed fracture, treatment protocols should be adjusted according to changes in epidemic risk.

Strategies for Precise Engineering and Conjugation of Antibody Targeted-nanoparticles for Cancer Therapy.

Improvements in the diagnosis and treatment of cancer are urgently needed for use in nanotechnology. Nanoparticles (NPs) can reduce the side effects of traditional chemotherapy by sustained release of loaded drugs and increase therapeutic efficiency. NPs can also enhance endothelial permeation retention by size effect and its accumulation in tumor cells through passive targeting. Furthermore, it is critical to treat cancer with a controlled targeted drug which can be specifically delivered into tumor cells and released there, resulting in a targeted therapy to eradicate tumor cells while sparing normal cells. To this end, antibody-mediated targeting therapy has been developed, but imperfections in antibodies (Abs) limit this therapy. Therefore, the combination of NPs and Abs has been highly valued in recent years, because conjugating special Abs on the surface of NPs can increase targeting efficiency, enabling selective delivery of anti-cancer drugs to tumor cells. In this mini-review, we would like to enumerate the strategies for the conjugation of Abs to the surface of the NPs as well as the precise engineering of targeted NPs. The application of targeting antibody fragments in this drug delivery system will also be discussed.

Mid-term outcomes of primary constrained condylar knee arthroplasty for severe knee deformity.

This study aimed to examine the clinical and radiographic outcomes of primary total knee arthroplasy (TKA) with use of NexGen® Legacy® Constrained Condylar Knee (CCK) prosthesis for severe knee deformity. Clinical data of 46 patients (48 knees in total, aged 61 years on average) with severe knee deformity who underwent TKA with NexGen® Legacy® CCK prosthesis between December 2007 and February 2012 were retrospectively analyzed. There were 34 knees with severe valgus with incompetent medial collateral ligament, 11 knees with severe flexion contracture with inability to achieve knee balancing in flexion and extension by posterior soft tissue release, 2 knees with Charcot arthritis with severe varus and bone loss, and 1 with traumatic osteoarthritis with severe varus and ligamentous instability. The mean duration of follow-up was 71 months (range 40-90 months). The New Knee Society scoring (NKSS) system and the Hospital for Special Surgery (HSS) score were used to evaluate the functional and clinical outcomes. Visual Analogue Scale (VAS) was used for pain measurement and Knee Society criteria for evaluation of radiological images. The results showed that, in the total 48 knees, 1 case of loosening due to short-stem tibial component at 3 months post-operatively underwent revision. The 6-year prosthesis survival rate in this cohort was 97.9%. There was no component infection occurring within 6 years. Significant post-operative improvements were found in NKSS and HSS scores. Patient satisfaction was significantly increased. Pain score was decreased significantly. Total functional score was improved from 31.46±11.43 to 86.42±8.87, range of motion (ROM) from 42.42°±23.57° to 95.31°±23.45° and the flexion contracture from 5.31°±7.87° to 0.92°±1.80°. Preoperative radiographic study showed excessive valgus (≥7°) in 37 knees, and varus deformity in 3 knees. Post-operative femorotibial alignment was valgus 3.88°±1.76° in 48 knees. Antero/posterior (A/P) view of X-ray films showed 4 radiolucent lines (RLL) in 48 tibial components. It was concluded that TKA with CCK is effective for the treatment of the severe unstable knee that cannot be balanced by soft tissue.

Clinical result of structural augmentation with cannulated bone screws for the treatment of osteonecrosis of the femoral head.

OBJECTIVE: To evaluate the results of treatment of osteonecrosis of the femoral head by structural augmentation through a routine core decompression procedure combined with insertion of cannulated bone screws incorporating autogenous bone graft and biomaterial containing decalcified bone matrix. METHODS: From February 2002 to February 2005, 31 patients (33 hips) with femoral head necrosis were treated in our hospital using insertion of cannulated bone screws incorporating autogenous bone graft. There were 18 men and 13 women with an average age of 37 years (range, 27-49). The Steinberg classification was stage I for 20 hips (61%) and stage II for 13 hips (39%). Clinical and radiographic evaluations were performed on all patients. The patient's satisfaction was also assessed. RESULTS: All 31 patients (33 hips) were retrospectively studied after a mean follow-up of 38 months (range, 18-48). The average Harris hip score was 76 before surgery and 91 at the final follow-up. All patients stated that they were satisfied and had significantly reduced pain. According to the Harris hip score system, 21 cases were excellent, 8 good and 2 fair. No complications, such as wound infection, subtrochanteric fracture, neuropathy and deep vein thrombosis, were found. CONCLUSION: Structural augmentation using the insertion of cannulated bone screws incorporating autogenous bone graft is an effective option for Steinberg I-II stages of femoral head necrosis. Further study is needed to confirm mid- and long-term results.

Ectopic osteogenesis of mouse bone marrow stromal cells transfected with BMP 2/VEGF(165) genes in vivo.

OBJECTIVE: To evaluate the osteogenic efficacy of mouse bone marrow stromal cells (mBMSC) transfected with bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor 165 (VEGF(165)) genes. METHODS: pIRES-BMP2-VEGF(165) plasmid DNA was introduced into the mBMSC using a liposome-mediated method. The expression of BMP2 and VEGF(165) genes was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Transfected cells were injected into the thigh muscle pouches of four nude mice. The osteoinductivity activity of the transfected cells was evaluated by radiographic and histological analysis at 4 weeks after injection. RESULTS: The mRNA and proteins of both BMP2 and VEGF(165) were successfully expressed in mBMSC as confirmed by RT-PCR and immunohistochemical analysis. Ectopically formed bone tissue was clearly observed at 4 weeks after cell injection in the thigh muscle pouches of the nude mice. CONCLUSION: mBMSC transfected with BMP2 and VEGF(165) genes can induce ectopic osteogenesis.

[Assessment of the expression profile during the entochondrostosis of vascular endothelial growth factor in bone morphogenetic protein 2 induced osteogenesis].

OBJECTIVES: To examine the gene expression profile of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) during entochondrostosis of mice and explore the expression rules and effects between BMP-2 and VEGF, and to detect the expression of VEGF in BMP-2 induced entochondrostosis in vivo. METHODS: cDNA microarray technique with 34,000 genes was used to analyze the gene expression profiles during entochondrostosis in the limbs of mice embryo from E10 to E14. Pathway analysis of BMP-2 and VEGF was performed with GCOS1.2 software. An experimental model of femoral muscular pouch in 20 mice was adopted. The expression of VEGF was examined by in situ hybridization method and immunohistochemical method in BMP-2 induced entochondrostosis in vivo. RESULTS: The expression signals of VEGF mRNA and VEGF appeared in cytoplasm during condensation of mesenchymal cell. As the mesenchymal cells differentiated into precartilage, the expression signals decreased in mesenchymal cells, but increased in chondrocytes and kept getting denser in the process of cartilage maturity. The peak expression of VEGF mRNA and VEGF in the experimental group appeared on the 14th day, accompanied by numerous hypertrophic chondrocytes. When mature cartilage calcified and new bone trabecula formed, the expression of VEGF mRNA and VEGF decreased in chondrocytes, but still expressed moderately in the osteoblasts and osteocytes. CONCLUSIONS: The finding reveals a complex pattern of gene coexpression of BMP-2 and VEGF during the critical period of entochondrostosis. It's feasible for the clinical application of BMP-2 in orthopedics.

Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty.

BACKGROUND: Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. METHODS: Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. RESULTS: The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed. CONCLUSIONS: The hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capability than that of nanobone putty only.

Vertebral plate regeneration induced by radiation-sterilized allogeneic bone sheets in sheep.

OBJECTIVE: To evaluate the effects and mechanism of radiation-sterilized allogeneic bone sheets in inducing vertebral plate regeneration after laminectomy in sheep. METHODS: Twelve adult male sheep (aged 1.5 years and weighing 27 kg on average) provided by China Institute for Radiation Protection underwent L3-4 and L4-5 laminectomy. Then they were randomly divided into two groups: Group A (n=6) and Group B (n=6). The operated sites of L4-5 in Group A and L3-4 in Group B were covered by "H-shaped" freeze-drying and radiation-sterilized allogeneic bone sheets (the experimental segments), while the operated sites of L3-4 in Group A and L4-5 in Group B were uncovered as the self controls (the control segments). The regeneration process of the vertebral plate and the adhesion degree of the dura were observed at 4, 8, 12, 16, 20 and 24 weeks after operation. X-ray and CT scan were performed in both segments of L3-4 and L4-5 at 4 and 24 weeks after operation. RESULTS: In the experimental segments, the bone sheets were located in the anatomical site of vertebral plate, and no lumbar spinal stenosis or compression of the dura was observed. The bone sheets were absorbed gradually and fused well with the regenerated vertebral plate. While in the control segments, the regeneration of vertebral plate was not completed yet, the scar was inserted into the spinal canal, compressing the dura and the spinal cord, and the epidural area almost disappeared. Compared with the control segments, the dura adhesion degree in the experimental regenerated segments was much milder (P less than 0.01), the internal volume of the vertebral canal had no obvious change and the shape of the dura sack remained well without obvious compression. CONCLUSIONS: Freeze-drying and radiation-sterilized allogeneic bone sheets are ideal materials for extradural laminoplasty due to their good biocompatibility, biomechanical characteristics and osteogenic ability. They can effectively reduce formation of post-laminectomy scars, prevent recurrence of post-laminectomy spinal stenosis, and induce regeneration of vertebral plates.