Objective To review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury. Methods The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized. Results The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial. Conclusion The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury.
ObjectiveTo investigate the mechanism of muscle-derived cells (MDCs) in repairing sciatic nerve defects in mice by observing the early growth of damaged peripheral nerves.MethodsThe hind limb skeletal muscles of mice carrying enhanced green fluorescent protein (EGFP) was collected to extract and culture EGFP-MDCs to P1 generation for later experiments. Five-mm-long nerve defects were created in the right sciatic nerves of C57BL/6 mice to establish a peripheral nerve defect model. The two stumps of sciatic nerve were bridged with 7-mm-long polyurethane (PUR) conduit. For the MDC group, EGFP-MDCs were injected into the PUR conduit. The PUR group without EGFP-MDCs was used as the negative control group. At 1 and 2 weeks after operation, the proximal and distal nerve stumps of the surgical side were collected to generally observe the early growth of nerve. Immunofluorescence staining of S100β, the marker of Schwann cells, was performed on longitudinal frozen sections of nerve tissues to calculate the maximum migration distance of Schwann cells, and observe the source of the Schwann cells expressing S100β. Immunofluorescence staining of phosphorylated erb-b2 receptor tyrosine kinase 2 (p-ErbB2) and phosphorylated focal adhesion kinase (p-FAK) in transverse frozen sections of nerve tissue was performed to calculate the positive rates of both proteins.ResultsThe general observation showed that the proximal and distal stumps of the surgical side in PUR group were not connected at 1 and 2 weeks after operation, while the bilateral nerve stumps in the MDC group were connected at 2 weeks after operation. Immunofluorescence staining showed that the Schwann cells expressing S100β in proximal and distal nerve stumps of PUR group and MDC group was not connected at 1 week after operation. At 2 weeks after operation, the Schwann cells expressing S100β in the two nerve stumps of the MDC group were connected, but not in the PUR group. At 2 weeks after operation, the sum of the maximum migration distance of Schwann cells in the regenerated nerve in both two groups was significantly increased when compared with that in each group at 1 week after operation, and that of MDC group was significantly higher than that in the PUR group at both 1 and 2 weeks after operation, the differences were all significant (P<0.05). At 1 week after operation, the positive rates of p-ErbB2 and p-FAK in the proximal nerve stump of MDC group were significantly higher than those in PUR group (P<0.05). There was no significant difference in the positive rate of p-ErbB2 of proximal stump between the two groups at 2 weeks after operation (t=0.327, P=0.747), while the positive rate of p-FAK of MDC group was significantly higher than that of PUR group (t=4.470, P=0.000). At 1 and 2 weeks after operation, the positive rates of p-ErbB2 and p-FAK in the distal stump of MDC group were significantly higher than those in PUR group (P<0.05). At 1 and 2 weeks after operation, part of Schwann cells expressing S100β, which were derived from EGFP-MDCs, could be observed in the regenerated nerves of MDC group.ConclusionMDCs can promote the phosphorylation of ErbB2 and FAK in the nerve stumps of mice, and promote the migration of Schwann cells. MDCs can be differentiated into cells expressing the Schwann cell marker S100β, or as other cellular components, to involve in the early repair of peripheral nerves.
Objective To investigate the effect of natural hirudin which is appl ied locally on vein congestion of random pattern skin flap in porcine models. Methods Three Guangxi Bama miniature pigs, including male and female aged 6-8 months and weighing 10-15 kg, were employed to establ ish animal model of vein congestive. Six dorsal random pattern skin flaps (three on each side) were prepared on each animal, 14 cm × 4 cm in size. According to the pharmacologic manipulations which were administered immediately and at 1, 2, and 3 days after operation respectively, the eighteen flaps were divided randomly into 3 groups (six in each group). In group A, isotonic Na chloride was locally appl ied as control group. In group B, 3 mL of 20 ATU natural hirudin was locally appl ied at each flap. In group C, 3 mL of 40 ATU natural hirudin was locally appl ied at each flap. Macroscopic observation (at 1 and 10 days postoperatively) and histological observation (at 1 and 7 days postoperatively) were made, the ratio of wet weight to dry weight of the congestive tissue (at 3 and 7 days postoperatively), the temperature of the surface of congestive flap (at 5 days postoperatively) and local blood flow of the flap (by Color Doppler Ultrasound at 7 days postoperatively) were measured. The survival rate of skin flaps was determined at 12 days postoperatively. Results Macroscopic observation showed that congestion of the flaps had no significance among three groups immediately after operation (P gt; 0.05); at 1 day postoperatively, the length of the congestion of the flap in group A (9.68 ± 0.43) cm was significantly longer than that in group B (6.81 ± 0.53) cm and group C (8.51 ± 0.64) cm (P lt; 0.05), while there was no significant difference between group B and group C (P gt; 0.05); at 10 days postoperatively, the necrosis at the distal end of flap in group A and group C were significantly longer than that in group B (P lt; 0.05), while there was no significant difference between group A and group C (P gt; 0.05). The histological observation revealed that the degree of erythrocyte agglutination in dermis capillary and veinule in group A was more serious than that of group B at 1 day postoperatively, and there was l ittle collagen and granulation tissue in group A when compared with group B at 7 days postoperatively. The ratio of wet weight to dry weight: at 3 days postoperatively, the value in group A (3.94 ± 0.14) was significantly higher than that of group B (3.43 ± 0.14) and group C (3.60 ± 0.19) (P lt; 0.05), and there was no significant difference between group B and group C (P gt; 0.05); at 7 days postoperatively, the value in group A (3.61 ± 0.11) was significantly higher than that of group B (3.08 ± 0.13) and group C (3.34 ± 0.21) (P lt; 0.05), and there was no significant difference between group B and group C (P gt; 0.05). The surface temperature of the congestive flap was (36.64 ± 0.70)℃ in group A, (38.61 ± 0.42)℃ in group B and (37.50 ± 0.46)℃ in group C at 5 days postoperatively; showing significant difference between group A and groups B, C (P lt; 0.05), and no significant difference between group B and group C (P gt; 0.05). The Color Doppler Ultrasound showed that the image of blood flow was very l ittle in group A, the image of venous return and perforator artery could be seen in group B and the image of arterial blood flow could be detected in group C. The survival rate of skin flaps was 45% ± 7% in group A, 67% ± 4% in group B and 52% ± 4% in group C at 12 days postoperatively; showing statistically significant difference between groups B, C and group A (P lt; 0.05), but no statistically significant difference between group B and group C (P gt; 0.05). Conclusion Local appl ication of natural hirudin can significantly improve the congestion of random pattern skin flap in a porcine model.
ObjectiveTo investigate the effect of cells in the epimysium conduit (EMC) on the regeneration of sciatic nerve of mice.MethodsThe epimysium of the 8-week-old male C57BL/6J enhanced green fluorescent protein (EGFP) mouse was trimmed to a size of 5 mm×3 mm, and prepared in a tubular shape (ie, EMC). Some epimysia were treated with different irradiation doses (0, 15, 20, 25, 30, 35 Gy) to inhibit cells migration. Then the number of migrating cells were counted, and the epimysia with the least migrating cells were selected to prepare EMC. Some epimysia were subjected to decellularization treatment and prepared EMC. HE and Masson staining were used to identify the decellularization effect. Twenty-four C57BL/6J wild-type mice were used to prepare a 3-mm-long sciatic nerve defect of right hind limb model and randomly divided into 3 groups (n=8). EMC (group A), EMC after cell migration inhibition treatment (group B), and decellularized EMC (group C) were used to repair defects. At 16 weeks after operation, the midline of the regenerating nerve was taken for gross, toluidine blue staining, immunofluorescence staining, and transmission electron microscopy.ResultsAt 15 days, the number of migrating cells gradually decreased with the increase of irradiation dose. There was no significant difference between 30 Gy group and 35 Gy group (P>0.05); there were significant differences between the other groups (P<0.05). The epimysium after treatment with 35 Gy irradiation dose was selected for thein vivo experiment. After the decellularization of the epimysium, no nucleus was found in the epimysium and the epimysium could be sutured to prepare EMC. At 16 weeks after operation, the nerves in all groups were recanalized. The sciatic nerve was the thickest in group A, followed by group B, and the finest in group C. Immunofluorescence staining showed that the EGFP cells in group A were surrounded by regenerated axons. Toluidine blue staining and transmission electron microscopy observation showed that the number of regenerated axons and the thickness of regenerated myelin sheath in group A were significantly better than those in groups B and C (P<0.05). There was no significant difference between groups B and C (P>0.05).ConclusionThe cellular components of the epimysium participate in and promote the regeneration of the sciatic nerve in mice.
ObjectiveTo investigate the value of plasma microRNA-216 (miR-216) in patients with acute pancreatitis as a clinical biomarker to early identify severe acute pancreatitis (SAP).MethodsPatients with acute pancreatitis who admitted to the hospital within 48 hours after the onset of disease between September and November 2014 were enrolled in this study. Plasam and clinical data of all the patients were collected. MiR-216 in the plasma was detected using quantitative real time-polymerase chain reaction.ResultsA total of 25 patients were enrolled. The Ct value of plasma miR-216 in SAP patients (32.40±1.43) was significantly upregulated than mild acute pancreatitis (MAP) (35.85±1.91, P<0.05) and moderately severe acute pancreatitis (MSAP) patients (35.90±2.44,P<0.05), respectively. The area under receiver operating characteristic curve for plasmamiR-216 in predicting SAP was 0.792 (P<0.05), which did not differ much from other conventional parameters such as C-reactive protein, urinary nitrogen, and cytokines (P>0.05).ConclusionPlasma miR-216 is significantly upregulated in SAP patients compared with MAP and MSAP, but it shows no inferior efficiency than the investigated conventional predictors in predicting SAP.
Objective To assess the quality of published systematic reviews and meta-analyses on Traditional Chinese Medicine (TCM) published in Chinese journals. Methods We searched CNKI, CMB from January 1995 to December 2006 and The Cochrane Library (Issue 4, 2006) for systematic reviews and meta-analyses on TCM. We extracted details of the interventions used in the treatment and control groups, analyzed the validity of included studies and investigated whether the reports used QUOROM statement or not. Results We identified 111 reports, of which 1 on prevention, 1 on adverse events, 1 on risk factors and premonitory symptoms, 2 on physiochemical parameters, and 106 on effectiveness and safety assessment. In total, 42 types of diseases were involved, and 41 reports were related to cerebrovascular diseases. As for the investigated interventions, 25 studies assessed TCM and 12 assessed acupuncture. Two had no control intervention design control in the group, 15 did not describe the interventions in the control group, 50 used active control (26 for western medicine, 12 for Chinese medicine, 12 for western plus Chinese medicine), 14 used blank control, 17 used baseline control, 4 used sham acupuncture or acupoint injection control etc., 5 used placebo control and 4 used "mutual control". The interventions used in the treatment and control groups varied widely. The number of trials included in the reviews and meta-analyses ranged from 1 to 35, and 24 studies included non-randomized controlled trials. Of the 111 reports, 14 were Cochrane reviews, 16 did not assess the quality of included randomized trials and a further 22 performed only simple and nonstandard quality assessment of the included trials. None of the reviews or meta-analyses used the QUOROM statement to report their results. Conclusions Because of the unique characteristics of TCM, systematic reviews of TCM should focus on a specific topic, avoid the selection of too many drugs, address the target indications of the test drugs and pay attention on intervention evaluation. High quality systematic reviews of TCM are needed but they will only be produced through the concerted efforts of clinicians, TCM practitioners and methodologists.