The Role and Mechanism of Exosomes from Umbilical Cord Mesenchymal Stem Cells in Inducing Osteogenesis and Preventing Osteoporosis.

Mesenchymal stem cell (MSC) exosomes promote tissue regeneration and repair, and thus might be used to treat many diseases; however, the influence of microenvironmental conditions on exosomes remains unclear. The present study aimed to analyze the effect of osteogenic induction on the functions of human umbilical cord MSC (HucMSC)-derived exosomes. Exosomes from standardized stem cell culture (Exo1) and osteogenic differentiation-exosomes (Exo2) were co-cultured with osteoblasts, separately. Cell counting kit-8 assays, alkaline phosphatase and alizarin red staining were used to observe the exosomes' effects on osteoblast proliferation and differentiation. The levels of osteogenic differentiation-related proteins were analyzed using western blotting. Estrogen-deficient osteoporosis model mice were established, and treated with the two exosome preparations. Micro-computed tomography and hematoxylin and eosin staining were performed after 6 weeks. MicroRNAs in Exo1 and Exo2 were sequenced and analyzed using bioinformatic analyses. Compared with Exo1 group, Exo2 had a stronger osteogenic differentiation promoting effect, but a weaker proliferation promoting effect. In ovariectomy-induced osteoporosis mice, both Exo1 and Exo2 improved the tibial density and reversed osteoporosis in vivo. High-throughput microRNA sequencing identified 221 differentially expressed microRNAs in HucMSC-derived exosomes upon osteogenic induction as compared with the untreated control group. Importantly, we found that 41 of these microRNAs are potentially critical for MSC-secreted exosomes during osteogenic induction. Mechanistically, exosomal miRNAs derived from osteogenic induced-HucMSCs are involved in bone development and differentiation, such as osteoclast differentiation and the MAPK signaling pathway. The expression of hsa-mir-2110 and hsa-mir-328-3p gradually increased with prolonged osteogenic differentiation and regulated target genes associated with bone differentiation, suggesting that they are probably the most important osteogenesis regulatory microRNAs in exosomes. In conclusion, we examined the contribution of osteogenic induction to the function of exosomes secreted by HucMSCs following osteogenic differentiation in vitro and in vivo, and reveal the underlying molecular mechanisms of exosome action during osteoporosis.

Halo-vest reduction combined with anterior decompression and internal fixation for lower cervical spine fracture and dislocation / 中华创伤杂志

Objective To investigate the efficacy of lower cervical spine fracture and dislocation treated by Halo-vest reduction combined with anterior decompression and internal fixation.Methods From January 2009 to December 2012,26 cases of lower cervical spine fracture and dislocation underwent Halovest reduction combined with anterior decompression and internal fixation.There were 18 males and 8 females,aged 19-64 years (mean,42.1 years).Injury resulted from traffic crashes in 11 cases,high falls in 9,and hit by heavy objects in 6.Segment of injury was C5/6in 10 cases,C6/7in 9,C3/4in 4,and C4/5in 3.Prior to anterior decompression/internal fixation and fusion,the Halo-vest external fixation was performed.Neurological performance was evaluated after operation.Results All the patients were followed up for 24-36 months (mean,27.4 months).According to the X-ray films and CT scan at the final follow-up,the alignment of the cervical spine was maintained and the implanted bone was completely fused without internal fixation breaking or loosening.Preoperative neurological status according to the Frankel grading was grade A in 6 cases,grade B in 8,grade C in 7,and grade E in 2.After operation,there were 5 cases in grade A,3 in grade B,4 in grade C,5 in grade D,and 9 in grade E.All together,6 cases presented two-grade improvement in neurological status,13 one-grade improvement,and 5 no changes (P ＜ 0.05).Conclusion Halo-vest reduction combined with anterior decompression and internal fixation is safe and effective in treatment of lower cervical spine fracture and dislocation.

Influence of thoracic sympathetic block on patients with diabetes mellitus complicated heart failure / 心血管康复医学杂志

Objective: To observe curative effect of thoracic sympathetic block on patients with diabetes mellitus (DM) complicated cardiac chamber enlargement and heart failure (HF). Methods: A total of 76 DM patients with cardiac chamber enlargement and HF were randomly divided into routine treatment group (n=36) and epidural nerve block group (nerve block group, n=40, received thoracic epidural nerve block based on routine treatment), and four weeks were a course of treatment. Changes of left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDd), left atrial diameter (LAD), levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain natriuretic peptide (BNP) and glycosylated hemoglobin (HbA1c) were observed in two groups. Results: There were no significant difference in all indexes between two groups before treatment (P>0.05). After treatment, total effective rate of cardiac function improvement in nerve block group was significantly higher than that of routine treatment group (95% vs. 66.7%, P<0.05). Compared with before treatment, there were significant decrease in LVEDd [(71.63±9.26)mm vs. (65.4±8.12)mm] and LAD[(45.62±7.10)mm vs. (37.14 ±6.28)mm] (P<0.05 both), significant increase in LVEF [(31.3±11.46)% vs. (42.12± 10.42) % , P< 0.01], and significant decrease in levels of TNF-α [(73.55±16.36)ng/L vs. (28.35±10.08) ng/L], IL-6 [(17.62±5.47) ng/L vs. (7.88±2.29) ng/L], BNP[(13.49±2.94) ng/L vs. (6.28±2.28) ng/L] and HbA1c [(7.9±2.6) % vs. (6.8±1.9) %] in nerve block group after treatment, P<0.05 or <0.001; and levels of LVEF, TNF-α, IL-6 and BNP in nerve block group after treatment were significantly improved than those of routine treatment group, P<0.05 or <0.01. Conclusion: Thoracic sympathetic block can significantly decrease levels of neuroendocrine and inflammatory factors, improve cardiac function, and elevate quality of life in patients with diabetes mellitus complicated heart failure.

Combined therapy of implants internal fixation and Halo-vest external fixation for the treatment of subaxial cervical fracture-dislocation / 中国组织工程研究

BACKGROUND:There is controversial in choosing the treatment method for the treatment of traumatic subaxial cervical fracture-dislocation and spinal cord injury. OBJECTIVE:To evaluate the clinical effect of implant internal fixation and Halo-vest external fixation on the stability after treatment of subaxial cervical fracture-dislocation. METHODS:A retrospective analysis was conducted on 17 patients with subaxial cervical fracture-dislocation in the Department of Orthopedics, the Second Affiliated Hospital of Shantou University Medical Col ege between January 2009 to December 2011, including 13 male patients and 4 female patients, the age was ranged from 21-65 years, average 41.6 years. There were six cases of high fal ing injury, three cases of crush injury and eight cases of traffic accident injury. The hospitalization time after injury was 2 hours to 5 days, average 2.5 days. Al the patients received Halo-vest external fixation under local anesthesia, then distraction gradual y, and received anterior decompression graft and titanium screw fixation under reduction. The treatment effect was evaluated through Frankel classification and imaging examination. RESULTS AND CONCLUSION:Al the patients were fol owed-up for 12-24 months, average 15.4 months. Normal anteraposterior X-ray film showed fracture reduction, the cervical vertebra restored to the normal sequence and physiological curvature;CT showed graft fusion without internal fixation fracture and loosing; according to Frankel classification, marked effect (decreased for 2 grade) in five cases, effective (decreased for 1 grade) in 10 cases, and ineffective in two cases. Implant internal fixation combined with Halo-vest external fixation is safe and reliable in the instability fixation of subaxial cervical fracture-dislocation, and can better restore the spinal sagittal alignment.

Rotary self-locking intramedullary nail for treating long tubular bone fracture of extremities / 中国基层医药

Objective To evaluate the results of rotary self-locking intramedullary nail (RSIN) for treating long tubular bone fracture of extremities, and discuss the current problems. Methods One hundred and twenty-two patients with long tubular bone fracture of extremities,including 59 femoral fractures,57 tibial fractures and 6 humeral fractures,who had been treated by RSIN were retrospectively investigated. Results All of the patients achieved clin-ical healing,with an average time of 24 weeks. Nobody was found to appear maluniun,infection and the break of inter-nal fixture. Internal fixations were removed after the fracture healing,with an average time of 14 months. It was diffi-cult to remove the internal fixations in 5 cases, and one case refractured after removing the internal fixations. Conclu-sion RSIN has the advantages such as easy operation,less trauma,no pendulum effect,early motion after operation and so on, except the characters of general interlocking intramedullary nail such as anti-rotation, anti-crispition and anti-displacement.

Effect of Electroacupuncture on Expression of Interleukin-1β in Rats with Acute Spinal Cord Injury / 中国康复理论与实践

@#Objective To observe the changes of interleukin-1β (IL-1β) in spinal tissues of rats with acute spinal cord injury after electroacupuncture (EA) treatment, and its association with inflammatory reaction and apoptosis after spinal cord injury. Methods The spinal cord injury of all the rats was induced by a 10 g × 2.5 cm impact with the reformative Allen equipment. The IL-1β and caspase-3 in spinal nerves of rats were detected with immunohistochemistry, while the level of superoxide dismutase (SOD) and malondialdehyde (MDA) in spinal tissues with the Colourimetry, neuron apoptosis with the terminal deoxynucleotidyl transferase-mediated deoxyuredine triphosphate-biotin nick end labeling (TUNEL). Results At the end of EA therapy, the expression of IL-1β and caspase-3, the level of MDA, and the number of TUNEL positive cells in EA group were all significantly lower than those in the control group (P<0.01), and the activity of SOD was obviously higher (P<0.01). Conclusion The EA therapy can decrease the expression of IL-1β and caspase-3 in rats of acute spinal cord injury, and alleviate the inflammatory reaction and apoptosis after spinal cord injury.

Bone regeneration using an injectable calcium phosphate/autologous iliac crest bone composites for segmental ulnar defects in rabbits.

BACKGROUND: Treatment of segmental bone loss remains a challenge in skeletal repair. A major therapeutic goal is the development of implantable materials that will promote bone regeneration. OBJECTIVE: We evaluate bone regeneration in grafts containing different concentrations autologous iliac crest bone (ACB) particles, carried in a new injectable calcium phosphate cement (CPC), in ulnar bone defects in rabbits. METHODS: Large upper-mid-diaphyseal defects (10 mm) were created in the left ulnae of 60 skeletally mature New Zealand white rabbits. ACB concentrations of 0, 25, 50, 75, and 100% (by volume) in CPC were used to fill operated sites. Defect bridging was monitored by serial radiography at 4, 8, and 12 weeks post-operation. Samples were then examined histologically and by manual palpation to determine the extent of new bone formation. RESULTS: At 4 weeks, we observed more elaborate structures and extensive absorption in ulnae treated with mixtures containing low concentrations of ACB (such as 0% and 25% volume of ACB/CPC), compared with those treated with mixtures containing high concentrations of ACB (such as 75% and 100% volume of ACB/CPC). At 8 weeks, histomorphometry revealed increased trabecular area and volume in the group treated with high ACB concentrations compared with those treated with low ACB concentrations. At 12 weeks, complete cortical bridging and regeneration of marrow space were detected in groups treated with high concentrations of ACB, and the amount of new bone regeneration was greater in these groups than in those treated with low ACB concentrations. CONCLUSIONS: Treatment of rabbit ulnar defects with injectable CPC carrying an optimized concentration of ACB particles can lead to cortical bridging and bone marrow regeneration within 12 weeks.

Effects of electro-acupuncture on behavioral recovery and its molecular basis in chronic spinal cord injured rats / 中国康复理论与实践

@#ObjectiveTo study the therapeutic mechanisms of electro-acupuncture on chronic spinal cord injury in rats.MethodsA model of chronic spinal cord injury was made. After 60 days, the pressure installs were removed, and the animals were treated with electro-acupuncture. A quantitive analysis was carried out using Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB scale). The expression of Neurotrophin-3 (NT-3) and its receptor TrkC were observed through immunohistochemistrical method and western blotting.ResultsAfter spinal cord injury, enhanced NT-3 and TrkC immunoreactivities were evident in neurons and glial cells. Furthermore, they were diminished in the electro-acupuncture group. Meanwhile, both evoked potentials and BBB scales were improved after EA treatment (P<0.05). ConclusionThe treatment of electro-acupuncture may promote behavioral function recovery of experimental animals, and NT-3 and TrkC may take part in the recovery.

Effect of acupuncture on the expression of nerve transmitter and neurotrophic factor in rats with chronic spinal cord injury / 中国康复理论与实践

@# ObjectiveTo explore the mechanism of electro-acupuncture (EA) on chronic spinal cord injury.MethodsAn animal model of moderate chronic progressive compression on spinal cord was made. Then the animals were decompressed and treated with EA. The combined behavioral scores (CBS) were tested, and the expressions of choline acetyltransferase (ChAT), brain derived neurotrophic factor (BDNF) and its receptor TrkB on the section of the rat's spinal cord were examined with immunohistochemical method.Results90 days after injury, the CBS of EA group was significantly better than that of decompression group ( P<0.05) and the number of positive ChAT cells in ventral horn of spinal cord in EA group was more than that in decompression group (P<0.05). The expressions of BDNF and TrkB enhanced after injury were recovered in the EA group.ConclusionThe electro-acupuncture may be effect on chronic spinal cord injury in rats by influencing the expressions of BDNF and its receptor, and improvs the expression and activity of ChAT.

EFFECT OF HESPRIDIN AND AMINOGUANIDINE ON KIDNEY FUNCTION AND MORPHOLOGY IN STZ-INDUCED DIABETIC RATS / 中华内分泌代谢杂志

In this study, the effect of hespridin, a natural flavonoid, on renal function and morphology in streptozotocin induced diabetic rats was evaluated. The result was compared with that of aminoguanidine which can inhibit the formation of advanced glycosylation end products (AGEs) and can decreased diabetic complications in experimental diabetes. The results showed that excretion of urinary protein, and the content of AGEs and LPO decreased, while the mesangial expansion and basement membrane thickening were retarded in diabetic rats treated with hespridin. These indicate that hespridin plays the same protective role as aminoguanidine in inhibiting formation of AGEs, thus preventing the development of nephropathy in STZ induced diabetic rats.