Intraoperative single administration of neutrophil peptide 1 accelerates the early functional recovery of peripheral nerves after crush injury

Neutrophil peptide 1 belongs to a family of peptides involved in innate immunity. Continuous intramuscular injection of neutrophil peptide 1 can promote the regeneration of peripheral nerves, but clinical application in this manner is not convenient. To this end, the effects of a single intraoperative administration of neutrophil peptide 1 on peripheral nerve regeneration were experimentally observed. A rat model of sciatic nerve crush injury was established using the clamp method. After model establishment, a normal saline group and a neutrophil peptide 1 group were injected with a single dose of normal saline or 10 μg/mL neutrophil peptide 1, respectively. A sham group, without sciatic nerve crush was also prepared as a control. Sciatic nerve function tests, neuroelectrophysiological tests, and hematoxylin-eosin staining showed that the nerve conduction velocity, sciatic functional index, and tibialis anterior muscle fiber cross-sectional area were better in the neutrophil peptide 1 group than in the normal saline group at 4 weeks after surgery. At 4 and 8 weeks after surgery, there were no differences in the wet weight of the tibialis anterior muscle between the neutrophil peptide 1 and saline groups. Histological staining of the sciatic nerve showed no significant differences in the number of myelinated nerve fibers or the axon cross-sectional area between the neutrophil peptide 1 and normal saline groups. The above data confirmed that a single dose of neutrophil peptide 1 during surgery can promote the recovery of neurological function 4 weeks after sciatic nerve injury. All the experiments were approved by the Medical Ethics Committee of Peking University People's Hospital, China(approval No. 2015-50) on December 9, 2015.

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 inflammationrelated 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.

Reinnervation of spinal cord anterior horn cells after median nerve repair using transposition with other nerves

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect(2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.

Brain functional remodeling caused by sciatic nerve transposition repair in rats identified by multiplemodel 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).

Synovial sarcoma in the plantar region: A case report and literature review

BACKGROUND Synovial sarcoma (SS),a rare malignant soft tissue tumor whose histological origin is still unknown,often occurs in limbs in young people and is easily misdiagnosed.CASE SUMMARY We report a 24-year-old man who sought treatment for plantar pain thought to be caused by a foot injury that occurred 4 years prior.Currently,he had been seen at another hospital for a 1-wk history of unexplained pain in the left plantar region and was treated with acupuncture,a kind of therapy of Chinese medicine,which partly relieved the pain.Because of this,the final diagnosis of biphasic SS was made after two subsequent treatments by pathological evaluation after the last operation.SS is rarely seen in the plantar area,and his history of a left plantar injury confused the original diagnosis.CONCLUSION This study shows that pathological and imaging examinations may play a vital role in the early diagnosis and treatment of SS.

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,nondestmetive,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.

Effect of Systolic Cardiac Function on Passive Leg Raising for Predicting Fluid Responsiveness： A Prospective Observational Study

Background：Passive leg raising （PLR） represents a ＂self-volume expansion （VE）＂ that could predict fluid responsiveness,but the influence of systolic cardiac function on PLR has seldom been reported.This study aimed to investigate whether systolic cardiac function,estimated by the global ejection fraction （GEF） from transpulmonary-thermodilution,could influence the diagnostic value of PLR.Methods：This prospective,observational study was carried out in the surgical Intensive Care Unit of the First Affiliated Hospital of Sun Yat-sen University from December 2013 to July 2015.Seventy-eight mechanically ventilated patients considered for VE were prospectively included and divided into a low-GEF （〈20%） and a near-normal-GEF （〉20%） group.Within each group,baseline hemodynamics,after PLR and after VE （250 ml 5% albumin over 30 min）,were recorded.PLR-induced hemodynamic changes （PLR-△） were calculated.Fluid responders were defined by a 15% increase of stroke volume （SV） after VE.Results：Twenty-five out of 38 patients were responders in the GEF 〈20% group,compared to 26 out of 40 patients in the GEF 〉20% group.The thresholds of PLR-△SV and PLR-△ cardiac output （PLR-△CO） for predicting fluid responsiveness were higher in the GEF 〉20% group than in the GEF 〈20% group （△SV：12% vs.8%;△CO：7% vs.6%）,with increased sensitivity （△SV：92% vs.92%;△CO：81% vs.80%） and specificity （△SV：86% vs.70%;△CO：86% vs.77%）,respectively PLR-△ heart rate could predict fluid responsiveness in the GEF 〉20% group with a threshold value of-5% （sensitivity 65%,specificity 93%） but could not in the GEF 〈20% group.The pressure index changes were poor predictors.Conclusions：In the critically ill patients on mechanical ventilation,the diagnostic value of PLR for predicting fluid responsiveness depends on cardiac systolic function.Thus,cardiac systolic function must be considered when using PLR.Trial Registration：Chinese Clinical Trial Register,ChiCTR-OCH-13004027;http：//www.chictr.org.cn/showproj.aspx？proj=5540.