Zenggan Chen

Vascular Endothelial Growth Factor Upregulates Inducible Nitric Oxide Synthase Expression in the Muscle Flap Ischemia Model in the Rat

The purpose of this investigation was to elucidate the regulation of inducible nitric oxide synthase (iNOS) expression by vascular endothelial growth factor (VEGF) in a muscle flap ischemia model in rats. The gracilis muscle flap model was chosen. Sixty adult male Sprague Dawley rats were randomly divided into two groups (n = 30). After 4 hours ischemia, the experimental group received VEGF treatment, and the control group was given saline in the same fashion. At time intervals of 0, 2, 6, 12, and 18 hours (n = 6 for each time interval) after injection, tissue samples were biopsied for reverse transcriptase polymerase chain reaction, routine hematoxylin-eosin staining, and CD31 immunohistochemical staining. The result showed that iNOS expression is increased in the gracilis muscle flap ischemia model in rats compared with the control group within 6 hours after ischemia (p < 0.05). In the VEGF group, iNOS expression increased rapidly over the first 2 hours, but no statistically significant difference was observed at 12 and 18 hours between the two groups (p > 0.05). We concluded that the application of VEGF could maintain the structure of capillaries and upregulate iNOS expression during the first 6 hours after ischemia in the ischemic muscle flap of a rat model. These findings may provide the evidence to study the mechanism of VEGF in improving flap survival.

Study of sensory and motor fascicles in brachial plexus and establishment of a digital three-dimensional graphic model.

To investigate a 3-dimensional (3D) model of human brachial plexus including its topography of sensory and motor fascicles with the assistance of the computer technology, 2 brachial plexus were serially horizontally sliced. Each slice was stained by Karnovsky–Roots acetylcholinesterase histochemical method. The stained sections were scanned, and the image was put into the computer serially. At last, the 3D diagram of brachial plexus was made. The internal structure of the brachial plexus was found to be very complicated. The fascicles bifurcated and recombined with one another with no fixed rules. All fascicles were mixed sensory and motor fibers. Acetylcholinesterase histochemical staining from a serial tissue section is a useful technique to distinguish sensory fibers from motor ones. The 3D visualization of the brachial plexus may help to develop a computerized database of the fascicle topography to provide an anatomical reference in fascicular repair of brachial plexus.

Surgical Decompression in the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-analysis.

Background Over the last decade, surgical decompression procedures have been commonly used in the treatment of diabetic peripheral neuropathy. However, the effectiveness of them remains to be proved. Methods A comprehensive literature search of databases including PubMed‐Medline, Ovid‐EMBASE, and Cochrane Library was performed to collect the related literatures. The Medical Subject Headings used were “diabetic neuropathy,” “surgical decompression,” and “outcomes.” The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Analyses were performed with Review Manager (Version 5.3, Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014). Results A total of 12 literatures (including 8 prospective and 4 retrospective) encompassing 1,825 patients with DPN were included in the final analysis. Only one literature was identified as a randomized controlled trial. The remaining 11 literatures were observational studies; 7 of them were classified as upper‐extremity nerve decompression group and 4 of them were classified as lower‐extremity nerve decompression group. Meta‐analysis shows that Boston questionnaire symptom severity and functional status of upper extremities, and distal motor latency and sensory conduction velocity of median nerve of DPN patients are significantly improved after carpal tunnel release. Besides, visual analog scale and two‐point discrimination are considered clinically and statistically significant in lower extremities after operation. Conclusions The findings from our review have shown the efficacy of surgical decompression procedures in relieving the neurologic symptoms and restoring the sensory deficits in DPN patients. As there are few high‐quality randomized controlled trials or well‐designed prospective studies, more data are needed to elucidate the role of surgical procedures for DPN treatment in the future.

Molecular Mechanism of the “Babysitter” Procedure for Nerve Regeneration and Muscle Preservation in Peripheral Nerve Repair in a Rat Model

Objective To investigate the molecular mechanism of nerve “babysitter” for nerve regeneration and muscle preservation in peripheral nerve repair. Methods Eighty rats were equalized into 4 groups: peroneal nerve transected, group A received no treatment; group B underwent end-to-end repair; group C underwent end-to-side “babysitter” with donor epineurial window; group D underwent end-to-side “babysitter” with 40% donor neurectomy. During second-stage procedure, end-to-end neurorrhaphies were executed in groups A, C, and D. Expression of Insulin-like growth factor (IGF)-1 in spinal cord and IGF-1, TNF-like weak inducer of apoptosis (TWEAK), and Fn14 in anterior tibial muscles were evaluated by histopathology at 4-, 8-, 12-, and 24-week timepoints postoperatively. Results At 4 weeks, group D expressed comparable IGF-1 with group B, and greater value than groups A and C in spinal cord. By 24 weeks, groups B and D showed higher values than groups A and C. Insulin-like growth factor 1 in muscles were greater in groups C and D than in groups A and B at 4 weeks, and comparable in all groups at 24 weeks. At 4 weeks, immunoreactive scores of TWEAK were 9.00 ± 0, 3.00 ± 0, 6.75 ± 0.75, and 6.75 ± 0.75, respectively. No differences were noticed in all groups by 24 weeks. At 4 weeks, Fn14 were similar in groups A, C, and D, but lower in group B. Group D showed comparable Fn14 with groups B and C, but lower value than group A at 24 weeks. Conclusions End-to-side nerve “babysitter” in peripheral nerve could promote fiber regeneration and muscle preservation by regulating expression of IGF-1 and TWEAK-Fn14. End-to-side “babysitter” with partial donor neurectomy could achieve comparable effects with end-to-end repair.

Expression of Livin and PlGF in human osteosarcoma is associated with tumor progression and clinical outcome

Baculoviral IAP repeat containing 7 (BIRC7/Livin/ML-IAP/KIAP; referred to as Livin throughout the present study) and placental growth factor (PlGF) are not detectable in the majority of normal differentiated tissues, but are present in a number of types of cancer, including hepatocellular carcinoma, ovarian cancer and renal cell carcinoma. The aim of the present study was to assess the expression levels of Livin and PlGF in human osteosarcoma specimens and cell lines, and to analyze the functions of Livin and PIGF in the prognosis of osteosarcoma. The expression levels of Livin and PlGF in 48 osteosarcoma specimens and three osteosarcoma cells were determined using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. The positivity rates of Livin and PlGF in osteosarcoma specimens were 58.3 and 60.4%, respectively, but were 0% in normal bone tissues. The expression levels of Livin and PlGF were increased in MG-63 cells, compared with those in the other cell lines evaluated in the present study. In addition, the expression levels of Livin and PlGF were significantly associated with tumor diameter and Enneking staging, but were independent of tumor site, age and sex of patients. The expression level of Livin was not associated with PlGF. Furthermore, the 5-year overall survival rate was decreased in the Livin or PlGF expression group, compared with that in the non-expression group (P=0.034 and P=0.012, respectively). The expression levels of Livin and PlGF were independent prognostic factors for patients with osteosarcoma. The results of the present study demonstrated that Livin and PlGF may participate in the pathogenesis of osteosarcoma. Therefore, pharmacological inhibition of Livin or PlGF may provide a novel strategy for osteosarcoma treatment.

Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling

Objective This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling. Methods Chronic nerve compression was created in streptozotocin (STZ)‐induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed. Results Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions. Conclusion Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN.

Burn-related peripheral neuropathy: A systematic review

Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified.

Different Recipient Vessels for Free Microsurgical Fibula Flaps in the Treatment of Avascular Necrosis of the Femoral Head: A Systematic Review and Meta-analysis

Background Several recipient vessels can be used in free microsurgical fibula flaps (MFFs) for the treatment of avascular necrosis of the femoral head (ANFH). Few articles investigate the influence of different recipient vessels on outcomes of MFF for ANFH. Methods A comprehensive literature search of databases including PubMed-Medline, Ovid-Embase, and Cochrane Library was performed to collect the related studies. The Medical Subject Headings used were “femur head necrosis” and “bone transplantation.” The relevant words in title or abstract included but not limited to “fibula flap,” “fibular flap,” “vascularized fibula,” “vascularized fibular,” “free fibula,” “free fibular,” “femoral head necrosis,” “avascular necrosis of femoral head,” and “ischemic necrosis of femoral head.” The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Results Finally, 15 studies encompassing a total of 1267 patients (1603 hips) with ANFH were pooled in the overall analysis. Recipient vessels for MFF included the ascending branch of the lateral circumflex femoral artery and vein in 8 studies, descending branch of the lateral circumflex femoral artery and vein in 2 studies, second perforating branch of the deep femoral artery and vein in 4 studies, and inferior gluteal artery and vein in 1 study. Preoperative and postoperative average Harris hip score and pooled analyses of the rate of conversion, radiographic progression, and hip surgery–related complications showed no significant difference on the outcomes of MFF on ANFH between using different recipient vessels. Conclusions Different recipient vessels did not affect outcomes in MFF procedures for ANFH. High-quality randomized controlled trials and prospective studies would be necessary to clarify reliable advantages and disadvantages between different recipient vessels. Until then, surgeons are justified in using ascending branch of the lateral circumflex femoral artery and vein, descending branch of the lateral circumflex femoral artery and vein, second perforating branch of the deep femoral artery and vein, and inferior gluteal artery and vein vessels according to care circumstances and customary practice.

Efficacy and Safety of the Babysitter Procedure With Different Percentages of Partial Neurectomy

Background After 2 months of denervation, the number of motor units in the muscle decreases; after 6 months of denervation, muscle atrophy and weakness are irreversible and successful nerve reconstruction does not generally restore function. The babysitter procedure was reported to successfully avoid muscle atrophy. One study found that the babysitter procedure with a 40% neurectomy was most suitable; however, the amount of donor nerve that can be borrowed for the babysitter procedure in peripheral nerve injury is unknown. Method One hundred adult female Sprague-Dawley rats were used in this study. The rats were randomly allocated to 5 groups (groups A–E; n = 20 each). The rats underwent different surgeries based on their grouping. At 6, 12, 18, and 24 weeks after surgery, 5 rats in each group were selected for electrophysiology and muscle force tests. These rats were then killed, and the gastrocnemius and tibialis anterior muscles were harvested for weight measurement and cross-sectional muscle measurement. Result The results of the effects on the peroneal nerves and tibialis anterior muscles after the babysitter procedure with 40% and 80% neurectomies showed that the functional ability of the recipient nerves was maintained and the muscle was effectively prevented from atrophy, whereas the 20% neurectomy and end-to-side procedures showed relatively poor performance. The results of the effects on the tibial nerve and gastrocnemius muscles after the babysitter procedure with 20% and 40% neurectomies showed that there was little effect on the donor nerve. By contrast, 80% neurectomy strongly and negatively affected the donor nerve. Conclusions Our results indicate that the babysitter procedure using a donor nerve with a partial neurectomy of 40% was the best choice for effectively treating peripheral (peroneal) nerve injury in rats.

Three-dimensional reconstruction of human median, ulnar and radial nerve

This study was undertaken to implement the three-dimensional (3D) reconstruction of the intraneural structure in the upper limb peripheral nerves. Three fresh cadaver peripheral nerves (one median, one ulnar and one radial nerve) were located with human hair, embedded in OCT, sectioned consecutively every 100 mum at a 20 mum thickness. Then all slices were stained with the acetylcholinesterase histochemical (AChe) method. 2D information of these slices were obtained through high resolution scanner. A special software (3D nerve visualization system) was used for 3D reconstruction of these nerves. Finally, 3D microstructure inside these nerves were reproduced in the computer. 3D nerve visualization system can show exactly the 3D microstructure inside these nerves and the rules of the regrouping and redistribution of the fasciculus. In addition, the reconstructed nerves could rotate at any angle along any axis, which might help us to observe the shape, position and relationships of fasciculus from different positions. It might do a great help to provide a anatomic basis for the approach in treating peripheral nerve injuries.