A special healing pattern in stable metaphyseal fractures.

BACKGROUND AND PURPOSE: Metaphyseal fractures heal in a rapid fashion that is different from the bone shaft healing process. Animal studies have focused on diaphyseal fractures. We investigated the metaphyseal fracture-healing process in rabbits. ANIMALS AND METHODS: 60 rabbits (divided into 12 groups) underwent proximal tibial osteotomy, anatomical reduction, and fixation with screws. After surgery, the proximal tibiae were harvested at different time points for histology. RESULTS: No obvious osteonecrosis or bone resorption were found 2 weeks after surgery. From day 5 to week 5, woven bone or new trabeculae formed. From week 2, remodeling into lamellar bone started and reached a peak at week 6. These 3 stages overlapped. Histomorphometry showed that the structure changed as a unimodal curve. INTERPRETATION: The healing process of metaphyseal fractures appears to differ from the commonly studied healing process in diaphyseal fractures. It is rapid, and can be divided into 4 histological stages: cellular activation and differentiation, formation of woven bone, transformation of woven bone into lamellar bone, and further remodeling.

[Nerve baby-sitter in reverse end-to-side neurorrhaphy preserves the structure of denervated muscle in rats].

OBJECTIVE: To explore the protected effect of sensory baby-sitter in reverse end-to-side fashion on denervated muscle. METHODS: The tibial nerve of twelve female adult Sprague Dawley rats was transected. Six animals served as controls. In the other rats, the end of the sural nerve was connected to the side of the distal tibial nerve stump. After twelve weeks, the wet weight, cross-sectional area, motor endplate perimeter from gastrocnemius muscle were examined. RESULTS: The difference in wet weight between the experimental group and the control group was statistically significant (39.2% ± 6.8% vs. 19.5% ± 4.3%, P<0.05). Histological observation of the unprotected muscles displayed wide areas of atrophied fibers and considerable connective tissue hyperplasia, whereas the structure of the experimental rats was preserved and there was only a slight increase in connective tissue. The average cross-sectional area and motor endplate perimeter of muscle fibers were significantly larger in the experimental group than in the control group [(1 148.85 ± 547.18) µm² vs. (575.05 ± 140.51) µm², (102.84 ± 53.29) µm vs. (59.60 ± 26.71) µm, respectively]. CONCLUSION: Sensory baby-sitter in reverse end-to-side neurorrhaphy preserves the structure of denervated muscle in rats.

[Generation and characterization of peripheral nerve animal model of pure motor/sensory nerve fibers].

OBJECTIVE: To generate peripheral nerve animal model of pure motor nerve fibers/pure sensory nerve fibers, and identify them. METHODS: The SPF SD rats were adopted in this study, and divided into 3 groups. In group A, we ablated L2-L4 ventral roots (VRs) to generate peripheral nerve animal model of pure sensory fibers. In group B, we ablated L2-L4 dorsal root ganglions (DRGs) to generate peripheral nerve animal model of pure motor fibers. Two time end-points were set as 2 weeks and 4 weeks. Neuron cells in lumbar spinal cords were detected by immunohistochemical staining with antibody of neuronal nuclei (NeuN). Motor neuron cells in lumbar spinal cords of pure motor fiber animal models and sensory neuron cells in lumbar spinal cords of pure sensory fiber animal models were counted respectively, and then compared to that of normal animals. Femoral nerves distal to the furcation were stained in osmium tetroxide, and then myelinated nerve fibers in the muscle branch and cutaneous branch of femoral nerve were counted respectively. RESULTS: The mean numbers of sensory neuron cells and motor neuron cells in normal lumbar spinal cords were 62.57 ± 1.02 and 29.73 ± 3.03 per 10 × 20 visual field respectively. For different end-points, the mean numbers of sensory neuron cells after ablating vental foots were 62.12 ± 1.77 (2 weeks), 62.15 ± 1.32 (4 weeks) per 10 × 20 visual field respectively; the mean numbers of motor neuron cells after ablating DRGs were 30.12 ± 0.44 (2 weeks), 30.00 ± 1.87 (4 weeks) per 10 × 20 visual field respectively. In group A, motor axons in muscle branch were degenerated as the sensory axons in muscle branch and cutaneous branch were not changed. The senory axons in femoral nerve for the two end-points were 1 558.17 ± 50.14 (2 weeks) and 1 544.00 ± 47.42 (4 weeks). In group B, sensory axons in muscle branch were degenerated as the motor axons were reserved. The motor axons in muscle branch for the two end-points were 387.67 ± 48.50 (2 weeks) and 393.50 ± 27.86 (4 weeks). There was no statistically significant difference in these mean numbers for the two end-points. The degenerating axons and myelin sheath had not been totally eliminated by the endpoint of 2 weeks. CONCLUSION: Peripheral nerve animal model of pure motor fibers can be generated by ablating L2-L4 DRGs; peripheral nerve animal model of pure sensory fibers can be generated by ablating L2-L4 ventral roots. The degenerating axons and myelin sheath have been totally eliminated by the end-point of 4 weeks. Ablating the ventral roots does not influence the survival of sensory neuron cells; and ablating the DRGs does not influence the survival of motor neuron cells.

[Radix hedysari extract promotes peripheral nerve regeneration].

Treatment of peripheral nerve injury is a major challenge in clinical practice. With advances in molecular biology and development of microsurgical techniques and tissue engineering, peripheral nerve repair procedures have been greatly improved. In the last 10 decades, most treatments for peripheral nerve injury in animal models have achieved histological and functional recovery, the treatments in humans, however, produce insufficient recovery, especially for proximal nerve injury. Increasing attention has been paid to the Traditional Chinese Medicine (TCM) for promoting peripheral nerve regeneration, since these remedies often display effective clinical outcome, minor side effects and effectiveness for multiple targets. Although TCM has complex ingredients and the specific pharmacological mechanisms for their effectiveness are still unclear, an effective clinical outcome is welcomed by many clinicians. In the past 20 years, we have made a series of detailed studies including the toxicity tests, pharmacodynamic tests, pharmacological experiments etc, about a new traditional formula which mainly contains the Radix hedysari, Epimedium etc. RESULTS have shown that this formula is safe to be used in both animals and humans with no toxicity and adverse effect, and systemic administration of this formula could enhance the peripheral nerve regeneration.

[Pain assessment of biological conduit small gap tubulization in rat sciatic nerve multilation model].

OBJECTIVE: To explore the pain sensation recovery discipline of 2 mm small gap biological conduit tubulization and epineurial neurorrhaphy in rat sciatic nerve multilation model. METHODS: Based on the rat sciatic nerve multilation model, 2 mm small gap biological conduit tubulization and epineurial neurorrhaphy were applied and the 50% paw withdrawal threshold was observed after 2, 4, 5, 6, 8 and 12 weeks. The data were analyzed by two-way ANOVA and chi-square criterion. RESULTS: Obvious hyperalgesia was observed in week 2 in both experimental group and control group, and 50% paw withdrawal threshold was improved significantly even to 15 g. The 50% paw withdrawal threshold began to decline week 4 and the 50% paw withdrawal threshold of small gap tubulization group was obviously lower than that of control group, which may imply that the pain sensation recovery of small gap tubulization group was earlier than that of control group. The 50% paw withdrawal threshold of small gap tubulization group began to increase to the plateau period [week 5: (12.70 ± 5.64) g; week 6: (12.20 ± 3.26) g; week 8: (12.31 ± 4.19) g; week 12: (13.95 ± 2.58) g]. The 50% paw withdrawal threshold of control group declined gradually [week 5: (10.47 ± 7.02) g; week 6: (9.42 ± 6.86) g; week 8: (8.50 ± 7.15) g; week 12: (8.06 ± 5.93) g]. The difference was statistical significant between small gap tubulization group and control group in 12th week. CONCLUSION: Compared with the traditional epineurial neurorrhaphy for peripheral nerve multilation, 2 mm small gap biological conduit tubulization can improve the 50% paw withdrawal threshold during peripheral nerve regeneration process and reduce the pain incidence.

Experimental study on the repair of tibial plateau defect.

OBJECTIVE: To evaluate the effect of autograft bone, allograft bone, calcium sulfate bone cement, and calcium phosphate bone cement on the repair of tibial plateau defect in rabbits. METHODS: We used autograft bone, allograft bone, calcium sulfate bone cement, and calcium phosphate bone cement to repair tibial plateau defect in rabbits. Gross and histologic observations, X-ray examination, and biomechanical test were conducted at 1, 2, 4, 8 weeks after operation. RESULTS: X-ray examination found that the bone density was evidently reduced in calcium sulfate group at 8 weeks after operation; there were no marked changes in other groups. The maximal load measurements showed that autograft and allograft groups were greater than calcium sulfate and calcium phosphate groups at 1 and 2 weeks after operation. However at 4 and 8 weeks after operation, no significant difference was found among the four groups. In autograft and allograft groups, there was no significant difference in biomechanical intensity at 2, 4, and 8 weeks, but it was significantly higher than that at 1 week. In calcium sulfate and calcium phosphate groups, the outcome was ranked in descending order as 1 week less than 2 week less than 4 week equal to 8 week. Histologic examination found a great amount of new bones at 8 week in both autograft and allograft groups. In calcium sulfate group, calcium sulfate was almost absorbed and there were numerous bone trabeculations. There was a large amount of unabsorbed calcium phosphate in calcium phosphate group. CONCLUSION: At 1-2 weeks postoperatively, the biomechanical intensity is higher in autograft and allograft groups than calcium sulfate and calcium phosphate groups, but after 4-8 weeks, there is no significant difference among groups. At 1-2 weeks, the biomechanical intensity in all groups is increased, but at 4-8 weeks, there is no significant increase. The rates of absorption and bone formation are quicker in calcium sulfate group than calcium phosphate group.

[Establishment and evaluation of animal model for studying the effect of traumatic brain injury on bone fracture healing].

OBJECTIVE: To establish a stable animal model for studying the effect of traumatic brain injury on bone fracture healing. METHODS: Eighty adult male Sprague-Dawley rats were randomly divided into fracture combined brain injury group (A) and simple fracture group (B). Animals of the two groups were killed 6 hours, 1 week, 2 weeks, 1 month and 2 months after trauma, respectively. Their brain histopathology changes were observed and neurological severity scores (NSS, 0 through 25 from no injury to severe injury) determined to measure the brain injury after head trauma, and fracture-healing was assessed by measuring callus volume and X ray examination at the scheduled time points after trauma. The callus volumes were compared between the groups using independent-samples t test 1 week, 2 weeks, 1 month and 2 months after trauma respectively. A value of P<0.05 was considered statistically significant. RESULTS: Ninety percent of the rats of group A presented with hemiplegia and the mortality rate was 10% (4/40) . The survived rats developed decorticated flexion deformity of the forelimbs, with behavioral depression, and lost some reflexes and muscle tone. The NSS were 10.83±1.94, 9.33±0.82, 8.17±1.17, 7.83±0.75 and 8.07±0.82 with 6 hours, 1 week, 2 weeks, 1 month and 2 months after trauma, respectively. It showed that the animals received moderate head injury, which tended to be stable from 2 weeks after trauma. Brain pathology showed that blood brain barrier was destroyed, and neurons were degenerative and necrotic at and around the trauma sites. The callus volumes(unit: mm(3)) of the two groups 1 week, 2 weeks, 1 month and 2 months after trauma were 60.03±28.05 and 32.80±11.04, 78.54±15.16 and 51.36±23.02, 93.01±10.65 and 72.38±20.38, 115.26±40.00 and 60.30±13.34, respectively. The callus volumes of the two groups 2 weeks, 1 month and 2 months after trauma were statistically and significantly different (P values were 0.036, 0.006 and 0.01 respectively), and there was no difference 1 week after trauma (P=0.065). CONCLUSION: This model is capable of producing accurately quantified brain injury. The animal model is credible, stable and reproducible, so it is an effective platform for studying the effect of traumatic brain injury on fracture.

[Clinical effect observation of biodegradable conduit small gap tublization repairing peripheral nerve injury].

OBJECTIVE: To observe the clinical effect of biodegradable conduit small gap tublization to repair peripheral nerve injury. METHODS: In the study, 30 cases of fresh peripheral nerve injury in the upper extremities were recruited. After formally informed and obtaining the consent, the recruited patients were divided into the degradable chitin conduit tublization group (experimental group: 15 cases) and traditional epineurial neurorrhaphy group (control group: 15 cases). Their nerve functional recovery conditions were clinically observed according to the standard score methods provided by SHEN Ning-jiang and British Medical Research Council. The excellent and good rates of the overall nerve functional recovery were calculated. The electrophysiologic study was carried out after 6 months. RESULTS: Of the total 30 cases, 28 were followed up, and there were 14 cases in the degradable chitin conduit tublization group and traditional epineurial neurorrhaphy group. The operation procedure was very simple, and the mean suture time [(8.0±0.8) min] was 20% shorter than that of the traditional epineurial neurorrhaphy group [(10.0±0.6) min]. All the wounds in the degradable chitin conduit tublization group healed as expected without rejection, hypersensitive reaction or anomalous draining. Electrophysiology examination results after 6 months displayed that the sensory nerves conduction velocity recovery rate was 77.37% of the normal value, and motor nerve conduction velocity recovery rate was 70.09% in the degradable chitin conduit tublization group. The sensory nerves conduction velocity recovery rate was 61.69% of the normal value, and motor nerve conduction velocity recovery rate was 56.15% in the traditional epineurial neurorrhaphy group. The exact propability methods was applied in the comparison of sensory and motor nerve conduction velocity recovery rate, and there was no statistically significant of two groups(sensory nerve conduction velocity recovery rate P=0.678;motor nerve conduction velocity recovery rate P=0.695). The combinated functional recovery excellent and good rates after repair in the degradable chitin conduit tublization group were 78.57%, while 28.57% in the traditional epineurial neurorrhaphy group. The Fisher's exact probabilistic method was applied in the comparison of combinated functional recovery excellent and good rates, and there was statistically significant of two groups(P=0.021). CONCLUSION: The operation procedure of the degradable chitin conduit tublization is very simple and the clinical recovery effect is much better than that of the traditional epineurial neurorrhaphy. The biodegradable conduit small gap tublization methods to repair peripheral nerve injury has the possibility to substitute the traditional epineurial neurorrhaphy.

Vertebroplasty with high-viscosity cement versus conventional kyphoplasty for osteoporotic vertebral compression fractures: a meta-analysis.

BACKGROUND: To evaluate outcomes following percutaneous vertebroplasty with high viscosity cement (PVP-HVC) and percutaneous kyphoplasty (PKP) with normal-viscosity cement in patients with osteoporotic vertebral compression fractures (OVCFs). METHODS: Pertinent studies were retrieved by searching five electronic databases up to July 2021. Additional records were identified via hand-searching of related references. Risk ratio (RR) and weighted mean difference (WMD), with their 95% confidence intervals (CIs), were calculated. A trial sequential analysis (TSA) was done for cement leakage. RESULTS: Twelve studies, embracing 1050 patients with OVCFs, were included. PVP-HVC was superior to PKP with normal-viscosity cement regarding risk of cement leakage (RR: 0.67, 95% CI: 0.54-0.83, I2 : 45.1%) and operation time (WMD: -11.26, 95% CI: -14.78 to -8.34, I2 : 88.8%). However, TSA revealed that a sufficient level of evidence for leakage reduction may have yet to be reached. PKP groups had a significant decrease in Cobb's angles postoperatively (within 1 month, WMD: 2.68, 95% CI: 1.85-3.48, I2 : 0%; after 1 year, WMD: 2.68, 95% CI: 1.35-4.01, I2 : 0%). There are no significant differences between the two procedures pertaining to injected cement volume, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and risk of adjacent vertebral fractures. CONCLUSION: PVP-HVC and PKP with normal-viscosity cement are safe and effective treatments for the management of OVCF, but the former is superior to the latter in terms of procedure time. The potential of PVP-HVC in reducing cement leaks remains to be validated by more well-designed studies.

Chitin scaffold combined with autologous small nerve repairs sciatic nerve defects.

Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects, it has many clinical limitations. As an alternative, various tissue-engineered nerve grafts have been developed to substitute for autologous nerves. In this study, a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats. The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath, reduced atrophy of the target muscle, and effectively restored neurological function. When the epineurium of the small autogenous nerve was removed, the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation. These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds. The study was approved by the Research Ethics Committee of Peking University People's Hospital (approval No. 2019PHE27) on October 18, 2019.

Brain functional remodeling caused by sciatic nerve transposition repair in rats identified by multiple-model resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis.

Lower extremity nerve transposition repair has become an important treatment strategy for peripheral nerve injury; however, brain changes caused by this surgical procedure remain unclear. In this study, the distal stump of the right sciatic nerve in a rat model of sciatic nerve injury was connected to the proximal end of the left sciatic nerve using a chitin conduit. Neuroelectrophysiological test showed that the right lower limb displayed nerve conduction, and the structure of myelinated nerve fibers recovered greatly. Muscle wet weight of the anterior tibialis and gastrocnemius recovered as well. Multiple-model resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis revealed functional remodeling in multiple brain regions and the re-establishment of motor and sensory functions through a new reflex arc. These findings suggest that sciatic nerve transposition repair induces brain functional remodeling. The study was approved by the Ethics Committee of Peking University People's Hospital on December 9, 2015 (approval No. 2015-50).

Portion of a nerve trunk can be used as a donor nerve to reconstruct the injured nerve and donor site simultaneously.

This study aims to estimate the effects of using a portion of a nerve trunk to repair itself and the injured nerve simultaneously. Proximal 1/2 median nerve served as donor nerve to repair the distal 1/2 median and whole ulnar nerve. Four months postoperation, the number of myelinated axons and nerve conduction velocities of the distal half median and ulnar nerve were (2033 ± 135 and 24.6 ± 5.3 m/s) and (1138 ± 228 and 30.3 ± 7.2 m/s). It suggests that using a portion of a nearby nerve truck to reconstruct itself and the injured nerve simultaneously is a practical method for severe peripheral nerve injury.

Can "dor to dor+rec neurorrhaphy" by biodegradable chitin conduit be a new method for peripheral nerve injury?

This study aims to estimate the effects of using one donor nerve to repair the injured nerve and itself simultaneously by biodegradable chitin conduit. Proximal median nerve served as donor nerve to repair the distal median and whole ulnar nerve. Four months postoperation, the number of myelinated axons and nerve conduction velocities of the distal median and ulnar nerve were (2085 ± 215 and 24.4 ± 5.9 m/s), and (1193 ± 102 and 30.7 ± 11.2 m/s). Recovery of the tetanic muscle forces of the reinvervated muscles were also observed. It suggests that Dor to Dor+Rec neurorrhaphy is a practical method for severe peripheral nerve injury.

[Small-gap bridging technology for peripheral nerve injury repair and the new sleeve material].

The peripheral nerve injury is a common injury in clinical practice. For centuries, traditional epineurial and perineurial suture techniques have been used to repair nerve transection after peripheral nerve injuries. As there are several types of nerve fibers in neural stump, accurate and effective regeneration of the fibers is limited. The outcome of repairing nerve injury has little improvement till now. Meanwhile , the selective regeneration of peripheral nerve fibers has been gradually confirmed by researchers. The limitation of traditional epineurial and perineurial suture techniques and the phenomenon of selective regeneration of nerve fibers had inspired us with the creative idea: the small-gap bridging suture techniques, which might take the place of the conventional epineurial and perineurial suture methods. We had made a series of detailed studies about this new method, devised a simple and reliable suture method and established an animal model of small-gap bridging suture technique. By observing peripheral nerve regeneration effect of nerve suture with small gap bridging by different gap lengths, we found that the optimal gap was between 1 to 3 mm, developed an artificial conduit with good biocompatibility and gradually applied this new conduit to mammals and primate animal experiments and clinical trials. All the studies obtained reliable results, which confirmed that the small-gap bridging suture was suitable to replace the traditional epineurium suture repairing the peripheral nerve injury. In 2010, this series of research gained the First Prize of Outstanding Scientific Achievement Award by the Ministry of Education.

[Effect of calcitonin gene-related peptide on RUNX2 expression in primary rat osteoblasts].

OBJECTIVE: To investigate the effects of exogenous calcitonin gene-related peptide (CGRP) on RUNX2 expression in primary cultured rat osteoblasts. METHODS: Primary cultured rat osteoblasts were obtained by collagenase / trypsinenzyme digestion from calvarial bone of neonate rats and were identified by ALP staining; The cells were exposed to gradient concentrations, and the effect of CGRP on the proliferation of osteoblasts was determined by MTT assay. The expressions of RUNX2 were quantified by RT-PCR and Western blotting after 48-hour exposure to different CGRP concentrations. RESULTS: CGRP could promote the proliferation of osteoblasts .When the concentration of CGRP were at 10(-8)-10(-6) mol/L, the proliferation rates of osteoblasts were 71.9%, 142.1%, 321.0%, respectively (P<0.05); when CGRP was at concentrations of 10(-7) and 10(-6) mol /L in osteoblasts for 48 h, the mRNA levels of RUNX2 was significantly increased, which increased (46.2±11.2)% and (58.6±14.0)% respectively (P<0.05); the expression of RUNX2 protein levels was consistent with the change of the mRNA levels. CONCLUSION: CGRP could promote RUNX2 expression in primary cultured rat osteoblasts, which suggests that RUNX2 is involved in the mechanism of osteoblast proliferation induced by CGRP.

[Neurofilament immune fluorescence staining: a new method for observing the morphology of the motor endplate].

OBJECTIVE: To investigate the effect of neurofilament (NF) immune fluorescence staining on observing morphology of the motor endplate. METHODS: Six SPF rats were used and their bilateral soleus muscles harvested under anesthesia. Then the samples were fixed with polyphosphate formaldehyde, and made frozen sections. Finally the neurofilament immunofluorescence staining was performed. The morphology of the motor endplate was observed under fluorescence microscope and laser scanning confocal fluorescence microscope. RESULTS: The claw-shape motor endplate was seen clearly under the fluorescent microscope and laser scanning confocal fluorescence microscope, and the images observed used to reconstruct the three-dimensional structure of motor endplate. CONCLUSION: Neurofilament immune fluorescence staining is a useful method for the morphology study of the motor endplate.

Combining CUBIC Optical Clearing and Thy1-YFP-16 Mice to Observe Morphological Axon Changes During Wallerian Degeneration.

OBJECTIVE: Wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury, and includes the disintegration and phagocytosis of peripheral nervous system cells. Traditionally, morphological changes are observed by performing immunofluorescence staining after sectioning, which results in the loss of some histological information. The purpose of this study was to explore a new, nondestructive, and systematic method for observing axonal histological changes during Wallerian degeneration. METHODS: Thirty male Thy1-YFP-16 mice (SPF grade, 6 weeks old, 20±5 g) were randomly selected and divided into clear, unobstructed brain imaging cocktails and computational analysis (CUBIC) optical clearing (n=15) and traditional method groups (n=15). Five mice in each group were sacrificed at 1st, 3rd, and 5th day following a crush operation. The histological axon changes were observed by CUBIC light optical clearing treatment, direct tissue section imaging, and HE staining. RESULTS: The results revealed that, compared with traditional imaging methods, there was no physical damage to the samples, which allowed for three-dimensional and deep-seated tissue imaging through CUBIC. Local image information could be nicely obtained by direct fluorescence imaging and HE staining, but it was difficult to obtain image information of the entire sample. At the same time, the image information obtained by fluorescence imaging and HE staining was partially lost. CONCLUSION: The combining of CUBIC and Thy1-YFP transgenic mice allowed for a clear and comprehensive observation of histological changes of axons in Wallerian degeneration.

Changes in proteins related to early nerve repair in a rat model of sciatic nerve injury.

Peripheral nerves have a limited capacity for self-repair and those that are severely damaged or have significant defects are challenging to repair. Investigating the pathophysiology of peripheral nerve repair is important for the clinical treatment of peripheral nerve repair and regeneration. In this study, rat models of right sciatic nerve injury were established by a clamping method. Protein chip assay was performed to quantify the levels of neurotrophic, inflammation-related, chemotaxis-related and cell generation-related factors in the sciatic nerve within 7 days after injury. The results revealed that the expression levels of neurotrophic factors (ciliary neurotrophic factor) and inflammation-related factors (intercellular cell adhesion molecule-1, interferon γ, interleukin-1α, interleukin-2, interleukin-4, interleukin-6, monocyte chemoattractant protein-1, prolactin R, receptor of advanced glycation end products and tumor necrosis factor-α), chemotaxis-related factors (cytokine-induced neutrophil chemoattractant-1, L-selectin and platelet-derived growth factor-AA) and cell generation-related factors (granulocyte-macrophage colony-stimulating factor) followed different trajectories. These findings will help clarify the pathophysiology of sciatic nerve injury repair and develop clinical treatments of peripheral nerve injury. This study was approved by the Ethics Committee of Peking University People's Hospital of China (approval No. 2015-50) on December 9, 2015.

Combining chitin biological conduits with small autogenous nerves and platelet-rich plasma for the repair of sciatic nerve defects in rats.

AIMS: Peripheral nerve defects are often difficult to recover from, and there is no optimal repair method. Therefore, it is important to explore new methods of repairing peripheral nerve defects. This study explored the efficacy of nerve grafts constructed from chitin biological conduits combined with small autogenous nerves (SANs) and platelet-rich plasma (PRP) for repairing 10-mm sciatic nerve defects in rats. METHODS: To prepare 10-mm sciatic nerve defects, SANs were first harvested and PRP was extracted. The nerve grafts consisted of chitin biological conduits combined with SAN and PRP, and were used to repair rat sciatic nerve defects. These examinations, including measurements of axon growth efficiency, a gait analysis, electrophysiological tests, counts of regenerated myelinated fibers and observations of their morphology, histological evaluation of the gastrocnemius muscle, retrograde tracing with Fluor-Gold (FG), and motor endplates (MEPs) distribution analysis, were conducted to evaluate the repair status. RESULTS: Two weeks after nerve transplantation, the rate and number of regenerated axons in the PRP-SAN group improved compared with those in the PRP, SAN, and Hollow groups. The PRP-SAN group exhibited better recovery in terms of the sciatic functional index value, composite action potential intensity, myelinated nerve fiber density, myelin sheath thickness, and gastrectomy tissue at 12 weeks after transplantation, compared with the PRP and SAN groups. The results of FG retrograde tracing and MEPs analyses showed that numbers of FG-positive sensory neurons and motor neurons as well as MEPs distribution density were higher in the PRP-SAN group than in the PRP or SAN group. CONCLUSIONS: Nerve grafts comprising chitin biological conduits combined with SANs and PRP significantly improved the repair of 10-mm sciatic nerve defects in rats and may have therapeutic potential for repairing peripheral nerve defects in future applications.

Identification of four differentially expressed genes associated with acute and chronic spinal cord injury based on bioinformatics data.

Complex pathological changes occur during the development of spinal cord injury (SCI), and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular targets and therapeutic strategies. This study was designed to explore differentially expressed genes (DEGs) associated with the acute and chronic stages of SCI using bioinformatics analysis. Gene expression profiles (GSE45006, GSE93249, and GSE45550) were downloaded from the Gene Expression Omnibus database. SCI-associated DEGs from rat samples were identified, and Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. In addition, a protein-protein interaction network was constructed. Approximately 66 DEGs were identified in GSE45550 between 3-14 days after SCI, whereas 2418 DEGs were identified in GSE45006 1-56 days after SCI. Moreover, 1263, 195, and 75 overlapping DEGs were identified between these two expression profiles, 3, 7/8, and 14 days after SCI, respectively. Additionally, 16 overlapping DEGs were obtained in GSE45006 1-14 days after SCI, including Pank1, Hn1, Tmem150c, Rgd1309676, Lpl, Mdh1, Nnt, Loc100912219, Large1, Baiap2, Slc24a2, Fundc2, Mrps14, Slc16a7, Obfc1, and Alpk3. Importantly, 3882 overlapping DEGs were identified in GSE93249 1-6 months after SCI, including 3316 protein-coding genes and 567 long non-coding RNA genes. A comparative analysis between GSE93249 and GSE45006 resulted in the enrichment of 1135 overlapping DEGs. The significant functions of these 1135 genes were correlated with the response to the immune effector process, the innate immune response, and cytokine production. Moreover, the biological processes and KEGG pathways of the overlapping DEGs were significantly enriched in immune system-related pathways, osteoclast differentiation, the nuclear factor-κB signaling pathway, and the chemokine signaling pathway. Finally, an analysis of the overlapping DEGs associated with both acute and chronic SCI, assessed using the expression profiles GSE93249 and GSE45006, identified four overlapping DEGs: Slc16a7, Alpk3, Lpl and Nnt. These findings may be useful for revealing the biological processes associated with SCI and the development of targeted intervention strategies.