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Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe -/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.
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Objective To investigate the clinical therapy of early internal fixation combined with perforator flap for forearm open fractures of Gustilo types Ⅲ B & Ⅲ C.Methods A retrospective study was conducted of the 45 patients with forearm open fracture of Gustilo type ⅢB or Ⅲ C who had been treated from July 2012 to October 2016 at Department of Traumatic Orthopaedics,The Ninth People's Hospital of Wuxi.They were 26 men and 19 women,aged from 20 to 61 years (average,41 years).Twenty cases were Gustilo type ⅢB and 25 Gustilo type ⅢC.By AO classification,8 cases were type A,21 ones type B,and 16 ones type C.The wound size ranged from 4 cm × 3 cm to 36 cm × 8 cm.Thirty-three patients were treated by primary internal fixation plus secondary transfer with a perforator flap,12 ones by secondary internal fixation plus transfer with a perforator flap.The period from injury to secondary flap transfer ranged from 5 to 20 days (average,12 days).In this series,36 anterolateral thigh perforator flaps,5 latissimus dorsal muscular flaps and 4 lateral arm flaps were transferred.Results All the 45 free flaps survived with no deep infection or osteomyelitis.Partial necrosis happened at the distal ends of 2 latissimus dorsal muscular flaps which were cured by skin graft.Postoperative circulatory crisis happened after transfer of an anterolateral thigh perforator flap which survived with 5 cm skin necrosis at the distal end after successful surgical exploration.Superficial wound infection happened in 12 patients with no deep or bone infection.All the patients were followed up for 12 to 36 months (average,18.5 months).All the flaps were soft in texture,with varying degrees of pigmentation.The sensory recovery was S2 in 8 flaps,S3 in 29 flaps,and S4 in 8 flaps.Obvious scar hyperplasis was observed at the donor site in 5 cases while no obvious scar hyperplasis was observed in the other 40 ones.All the fractures got united after 4 to 14 months (average,8.6 months).Nonunion happened in 2 patients who were treated with autologous iliac graft 8 months after operation.By Anderson criteria,the curative efficacy was assessed as excellent in 15 cases,as good in 21,as fair in 7 and as poor in 2,yielding an excellent to good rate of 80.0％.Conclusion Early internal fixation combined with perforator flap transfe is an effective strategy for treatment of forearm open fractures with soft tissue defects of Gustilo types Ⅲ B &Ⅲ C,due to its advantages of shortened treatment period,possibility for early rehabilitation,decreased complications and satisfactory functional recovery.
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Objective To investigate the clinical efficacy of free flap transplantation in repairing the Gustilo type ⅢB and ⅢC fractures of tibia and fibula combined with soft tissue defects.Methods A retrospective case series study was conducted on the clinical data of 46 patients who had Gustilo type ⅢB and ⅢC fractures of tibia and fibula with soft tissue defects admitted from June 2013 to January 2017.There were 34 males and 12 females,aged 1-67 years (mean,39 years).The wound defect areas ranged from 6 cm × 20 cm to 7 cm × 38 cm.According to the Gustilo fracture classification,there were 31 cases of type ⅢB and 15 cases of type ⅢC.According to the AO fracture typing,there were five cases of type A,23 type B,and 18 type C.All patients were repaired with free flap transplantation,among which 40 patients were treated with anterolateral thigh flap and six with latissimus dorsi flap.The areas of anterolateral thigh flap ranged from 6 cm × 13 cm to 14 cm ×32 cm,and those of the latissimus dorsi flap from 6 cm × 22 cm to 7 cm × 40 cm.Efficacy was evaluated by flap survival rate,complications,fracture healing time,lower limb function scoring system (LEFS),and skin flap function.Results All limbs were salvaged successfully.One case of total flap necrosis and eight cases of postoperative crisis occurred.After active exploration and treatment,three cases were seen distal local necrosis,and the total survival rate was 91％.Infection at the donor site was found in two cases.The complication incidence rate was 4％.All patients were followed up for 7-42 months,with an average of 19 months.The fracture healing time averaged 43.5 weeks,and the LEFS score averaged 54 points.According to the seven indexes of flap function,the results were excellent in 1 1 cases,good in 29 cases,fair in four cases,and poor in two cases,with an excellent and good rate of 87％.Conclusion Free flap transplantation can achieve satisfactory efficacy in treating Gustilo type ⅢB and ⅢC of tibia and fibula combined with soft tissue defects,with high limb salvage rate and good function recovery.
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Objective To explore the clinical application of antcrolateral thigh flap transplantation in repairing wound around the knee with descending genicular artery as the recipient vessel,when anterior or posterior tibial vessel could not be utilized.Methods From January,2015 to May,2017,free anterolateral thigh flaps obtained from anastomosis of descending genicular artery and great saphenous vein were transplanted to repair the skin soft tissue defect around the knee combined with tendon and bone exposure in 7 patients,after preoperative color Doppler sonography ultrasound (CDU) for precise positioning.There were 4 males and 3 females,with the flap area ranging from 18.0 cm×8.0 cm-38.0 cm×8.0 cm.All of the donor sites were sutured directly.Postoperative followedup was done termly.Results All the patients were followed-up for 6 to 14 months,with an average of 8.9 months.Typically,2 cases had large defect areas,with distal flap necrosis of 6.0 cm and 4.0 cm,respectively,which were resected and achieved secondary skin graft healing on the residual surface.Additionally,4 cases had completely survived flaps and achieved secondary skin graft healing on the residual surface.The remaining 1 case had completely survived flap,but the distal flap near the anteromedial tibia developed bone exposure as a result of the complicated osteomyelitis.As a result,the patient received gastrocnemius myocutaneous flap to repair the wound.Conclusion Anterolateral thigh flap transplantation in repairing skin soft tissue defect wound around the knee,with descending genicular artery as the recipient vessel,can achieve satisfactory clinical efficacy,which can serve as one choice for flap repair in wound around the knee.
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[Objective]To assess the effect of femoral head reshaped surgery for treatment of collapse stage of femoral head necrosis in dogs.[Method]Experimental femoral head necrosis models were made in unilateral femoral head of 10 adult dogs.Under anaesthesia,the necrotic mass in the collapse area of femoral head necrosis was fully curreted through a passage from femoral neck to callapse head,a self-designed ball-tube apparatus enveloped with a cannula was put into under the curreted area,normal saline injected to fill the ball in the collapse cavity till the collapse area forced to reshape a spherical femoral head;After withdraw of normal saline,bone cement of calcium phosphate was injected into the reshaped cavity to maintain the reshaped femoral head.Finally the ball-tube apparatus was taken out.Preoperative and postoperative X-ray film of femoral head were taken to evaluate the reshaping.Femoral heads of experimental side and normal femoral head of contralateral side as control were take out after the dogs sacrifice for biomechanical examination of maximum compression strength.[Result]In experimental group,as compared to preoperative radiograms,the postoperative radiograms of 10 dogs showed the curreted necrotic cavity was fully filled with bone cement and reshape was maintained.The maximum comopression strength of femoral heads of control group was 49 Mpa to 60 Mpa,and that of experimental group was 49~54 Mpa with no statistical significant difference.[Conclusion]Femoral head reshaping surgery may be a method of choice for treatment of collapse stage of femoral head necrosis in experimental animal,but long-term effect should be evaluated thereafter.
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BACKGROUND: Polymethylmethacrylate (PMMA) can ameliorate the condition between vertebral pedicle screws and peripheral bone-matrix interfaces and notably enhance the strength of screw fixation. However, there are several disadvantages during and after operation such as polymerized thermal damaging effect, toxicity and unabsorbable etc. Calcium phosphate cement (CPC) is biocompatible and biodegradable with good biosafty and produce no heat of polymerization, which is a perfect substitute for PMMA.OBJECTIVE: To evaluate the reinforcing effect of CPC on vertebral pedicle screw fixation at biomechanical aspect.DESIGN: Randomized control and repetitive observed measurement.SETTING: Department of Orthopaedics, Second Affiliated Hospital of Nanjing Medical University.MATERIALS: The experiment was conducted in Tongji Medical College of Huazhong University of Science and Technology from August of 2002 to February 2003. ①Two fresh spines from male bodies respectively aged of 52 and 50 years were provided by the Anatomic Department of Tongji Medical College. Ten vertebrae in each spine were obtained (T8-12, L1-5) and taken as 52-year group and 50-year group. Radiographs of these vertebrae were taken to exclude congenital abnormality, fracture, tumor or other pathological changes. Vertebrae in both groups were osteoporoses of grade I and in accordance with experimental requirement.②Main components of solid phase of CPC were micropowder of tricalcium phosphate and tetracalcium phosphate (TTCP) and its main ingredients of liquid phase was citrate solution, which was prepared with solid phase in the ratio of 1g vs 1 mL.Primarily setting-time was 15 minutes and the final setting-time was 12hours with the maximum compressive strength between 45 Mpa and 57 Mpa. ③Diameter of self-made pedicle screws was 5 mm; Length of screw thread segment was 34 mm; Pitch was 2 mm; Depth of screw thread was 0.8 mm.METHODS: ①Biomechanical test of pedicle screw fixation at final solid time of CPC: Vertebrae of 50-year group were taken as testing subjects.Control lateral: vertebral pedicle screws were implanted directly in screw path; Strengthening lateral: vertebral pedicle screws were inserted after fillingwith CPC. After that, specimens were deposited in a thermostated container for twelve hours at 37 ℃. Maximum axial pull-out strength of vertebral pedicle screw was determinated. ②Biomachanical test of vertebra pedicle screw fixation when CPC primarily hardened: specimens in 52-year group were taken as testing subjects. In the same way, vertebral pedicle screw was implanted in the control lateral of vertebral pedicle,while that in the strengthen lateral was implanted after filling of cement,which were placed in the thermostated container for 15 minutes at 37 ℃,the maximum axial pull-out strength of vertebral pedicle in primary setting time were determinated. ③Biomechanical test of CPC in the reinforcement of loose vertebral pedicle screw fixation: vertebrae in 50-year group were selected. Loosened vertebral pedicle screws were re-fixed with CPC for 12 hours. Maximum axial pull-out strength of bilateral screws was tested.MAIN OUTCOME MEASURES: ①Biomechanical testing results of pedicle screw fixation at final solid time of CPC. ②Biomechanical testing results of vertebral pedicle screw fixation when CPC primarily hardened.③Biomechanical testing results of CPC in the reinforcement of loose vertebral pedicle screw fixation.RESULTS: ①Medians of maximum axial pull-out strength of vertebral pedicle screws in control and strengthening laterals in the 50-year group were 620 N and 1 136 N respectively. Compared with control lateral, that in the strengthening lateral increased by 83 % (P ＜ 0.01). Median of anti-cutting stress increased from 1.16 N/mm2 to 2.13 N/mm2 after being strengthened. ②The medians of those in the 52-year group were 554.5 N and 859.5 N respectively and that in the strengthening lateral increased by 55 % in comparison with that in the control lateral (P ＜ 0.01).The median of anti-cutting stress of reinforced bone-screw interface increased from 1.03 N/mm2 to 1.61 N/mm2. ③Maximum axial pull-out strength of vertebral pedicle screws in control and strengthening laterals in the 50-year group of 12 hours after re-fixation were 517 N and 876 N, which respectively increased by 63.6% or 54.2% (P ＜ 0.01) in comparison with median of that of loose screw in the same lateral.CONCLUSION: CPC can enhance vertebral pedicle screw fixation in primary and final setting time, with which loosened screws can be re-fixed.Vertebral pedicle screw in control lateral and strengthening lateral strips from bone-screw interface without peripheral bone and vertebral pedicle being destroyed seriously, which are beneficial to the second insertion of screw.
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BACKGROUND: Bone marrow stromal cells(BMSCs) are the ideal gene target cells and will have a bright future in the gene therapy of spinal cord injury.OBJECTIVE :To detect the expression of glial cell line - derived neurotrophic factor(GDNF) gene after BMSCs were infected by adenovirus-medialed GDNF (Adv-GDNF) in vitro and to explore its biological activity.DESIGN: A randomized controlled trial study.SETTING: Laboratory of Orthopedic DepartmentMATERIALS: The experiment was completed in the Laboratory of Orthopedic Department, Affiliated Tongji Hospital of Tong ji Meidcal College,Huazhong University of Science and Technology. Twenty-four SD rats of either gender, weighing (180 ± 20) g.INTERVENTIONS: BMSCs were infected by Adv-GDNF in vitro and then cocultured with spinal cord dorsal root ganglion. The three methods, immunofluorescent chemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay(ELISA) were used to evaluate GDNF expression in the BMSCs. The biological activity of GDNF was observed by a phase contrast microscope.MAIN OUTCOME MEASURES:Primary outcomes:①RT-PCR;②results of immunofluorescent chemical examination;③biological activity of GDNF in vitro. Secondary outcomes:①culturing and identification of BMSCs②time-effect relationship of GDNF expression revealed by ELISA.RESULTS: Immunofluorescence displayed expression of GDNF in BMSCs 48hours after Adv-GNDF infection. RT-PCR analysis demonstrated expression of GDNF mRNA 24 hours after Adv-GNDF infection. ELISA confirmed the presence of GDNF in the liquid supernatant of BMSCs 24 hours after Adv-GDNF infectionn and showed that GDNF was secreted. The supernatant can promote the neurite outgrowth in the rat dorsal root ganglion(DRG).CONCLUSION: It is demonstrated that BMSCs infected by Adv-GDNF can express GDNF steadily and the expressed GDNF has the activity of promoting neurite outgrowth, which lays a foundation of the GDNF gene therapy for spinal cord injury.
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When the patients with senile or secondary osteoporosis are treated with screw fixation, the screws are likely to get loose or pulled out. Polymethylmethacrylate (PMMA) can enhance screw fixation strength to some extent in clinic, but PMMA has such disadvantages as irresorbability, polymeric heating effect and toxic reaction so that its clinical application is limited. Calcium phosphate cement, however, has drawn much attention because it gets rid of the shortcomings of PMMA. This article introduces recent progress made in research on fixation with calcium phosphate cement enhancing screw.
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By culturing bone marrow mesenchymal stem cells of rabbits with fibrin glue in vitro, the biocompatibility of fibrin glue was investigated to study whether this material can be used as scaffolds in bone tissue engineering. After 2-months old New Zealand rabbits had been anesthetized, about 4-6 ml of bone marrow were aspirated from rabbit femoral trochanter. The monocytes suspension was aspirated after bone marrow was centrifuged with lymphocyte separating medium and cultured primarily. Then the cells were divided into two groups: one was cultured with complete medium and the other with induced medium. The cells of the two groups were collected and inoculated to the culture plate containing fibrin glue. In the control group, cells were inoculated without fibrin glue. The implanted cells and materials were observed at different stages under a phase-contrast microscope and scanning electron microscope. MTT and alkaline phosphatase (ALP) were measured. Bone marrow mesenchymal stem cells grew on the surface of fibrin glue and adhered to it gradually. Cells light absorption value (A value) and the ALP content showed no significant difference. Fibrin glue had no inhibitory effect on cell morphology, growth, proliferation and differentiation. It has good biocompatibility and can be used as scaffold materials for bone marrow mesenchymal stem cells in bone tissue engineering.
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Biocompatible Materials/pharmacology , Bone Marrow Cells/cytology , Cells, Cultured , Coculture Techniques , Fibrin Tissue Adhesive/pharmacology , Mesenchymal Stem Cells/cytology , Tissue EngineeringABSTRACT
By culturing bone marrow mesenchymal stem cells of rabbits with fibrin glue in vitro, the biocompatibility of fibrin glue was investigated to study whether this material can be used as scaffolds in bone tissue engineering. After 2-months old New Zealand rabbits had been anesthetized, about 4-6 ml of bone marrow were aspirated from rabbit femoral trochanter. The monocytes suspension was aspirated after bone marrow was centrifuged with lymphocyte separating medium and cultured primarily. Then the cells were divided into two groups: one was cultured with complete medium and the other with induced medium. The cells of the two groups were collected and inoculated to the culture plate containing fibrin glue. In the control group, cells were inoculated without fibrin glue. The implanted cells and materials were observed at different stages under a phase-contrast microscope and scanning electron microscope. MTT and alkaline phosphatase (ALP) were measured. Bone marrow mesenchymal stem cells grew on the surface of fibrin glue and adhered to it gradually. Cells light absorption value (A value) and the ALP content showed no significant difference. Fibrin glue had no inhibitory effect on cell morphology, growth, proliferation and differentiation. It has good biocompatibility and can be used as scaffold materials for bone marrow mesenchymal stem cells in bone tissue engineering.