Free Chimeric Superficial Circumflex Iliac Artery Perforator Flap in Reconstructing the Distal Complex Extensor Tendon Injury.

SUMMARY: The distal complex extensor tendon injury, presenting as traumatic skin, zones 1 and 2 of extensor pollicis longus and extensor hallucis longus, and bony insertion loss, represents a challenging issue and requires a well-vascularized skin paddle, tendinous graft, and insertional reconstruction. Guided by the all-in-one-step reconstruction rule, the chimeric superficial circumflex iliac artery perforator (SCIAP) flap, generally considered as a promising multiple-type tissue provider (eg, vascularized skin paddle, fascia, iliac flap), can fulfill the reconstructive demands and has an edge over the two-stage countermeasure. The authors adopted tripartite SCIAP flaps to reconstruct distal complex thumb or toe injuries in eight cases (six thumbs and two halluces), all of which were reattached with vascularized fascia lata-iliac crest conjunctions using a pull-out technique. All SCIAP flaps survived uneventfully without donor-site complications. The remodeled interphalangeal joints regained nearly normal radiologic manifestation. The chimeric SCIAP flap may be a promising technique for distal complex extensor tendon injury; providing vascularized skin paddle and fascia lata-iliac crest graft, it also qualifies for the all-in-one-stage reconstruction concept. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The bone mesenchymal stem cell-derived exosomal miR-146a-5p promotes diabetic wound healing in mice via macrophage M1/M2 polarization.

A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro. Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo. The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.

Protein kinase D1 promotes the survival of random-pattern skin flaps in rats.

BACKGROUND: In reconstructive surgery, random skin flaps are commonly used tools to cover skin defects, however, their applicability and size are limited by post-operative complications such as marginal ischemia-reperfusion injury and flap necrosis. Protein kinase D1 (PKD1), a calcium/calmodulin-dependent serine/threonine kinase, is known to induce angiogenesis and has been shown to mitigate ischemia in cardiovascular diseases. However, the role of PKD1 has not been investigated in skin flaps. METHOD: Seventy-five male Sprague-Dawley rats with skin flaps were randomly divided into three groups: control, PKD1, and CID755673. Seven days following surgery, we assessed the general view and survival rate of the flap using histological analysis. Laser Doppler and lead oxide/gelatin angiography were used to evaluate microcirculation blood flow. Histopathological changes, neovascularization and microvascular density (MVD). were examined and calculated using microscopy after H&E staining. Protein expression levels were determined using immunoblotting and immunohistochemistry techniques. RESULT: PKD1 significantly improved flap survival by upregulating angiogenic factors VEGF and cadherin5 and increasing antioxidant enzymes SOD, eNOS, and HO1, as well as reducing caspase 3, cytochrome c, and Bax expression, and attenuating IL-1ß, IL-6, and TNF-α. In the PKD1 group, PKD1 increased neovascularization, and blood flow and flap survival areas were larger as compared to the control and CID755673 groups. CONCLUSION: These findings show that PKD1 accelerates angiogenesis, reduces oxidative stress, and impedes apoptosis and inflammation, thus resulting in improved flap survival. Our observations indicated that PKD1 could be a therapeutic target for flap failure treatment.

Risk Factors Associated With Misdiagnosis of Digital Glomus Tumor: A Retrospective Cohort Study.

OBJECTIVE: Glomus tumors are benign with unique triad of symptoms; however, the delayed diagnosis of these tumors is common. We investigated the possible risk factors for the misdiagnosis of digital glomus tumors, with an aim to treat these patients on time. METHODS: We conducted a retrospective cohort study of 104 patients with digital glomus tumors from October 2009 to February 2021. Data pertaining to sex, age, tumor locations, symptoms, imaging modalities, and clinical departments visited by the patients were extracted and analyzed through logistic regression. RESULTS: The duration of delayed diagnosis ranged from 3 months to 40 years (mean, 5.5 ± 6.5 years). The total misdiagnosis and recurrence rate are 34.6% and 3.8%, respectively. On the multivariate logistic regression, the misdiagnosis of digital glomus tumor was significantly associated with the clinical departments visited by the patients ( P < 0.001). The risk of misdiagnosis of nonhand surgery department visit is 179.741-fold higher than that of hand surgery department visit. CONCLUSIONS: The misdiagnosis rate of digital glomus tumor was closely related to the clinical departments visited by the patients. Hand surgeons are the first choice for the treatment of the tumor.

Melatonin promotes peripheral nerve repair through Parkin-mediated mitophagy.

Schwann cells (SCs) are the major glial cells in peripheral nervous system. They unsheathe and myelinate axons and play an essential role in peripheral nerve regeneration. Several studies report that Parkin-mediated mitophagy is associated with various diseases. Melatonin promotes proliferation of central glial cells. Little is known about the effect of melatonin and Parkin-mediated mitophagy on peripheral nerve repair. In this study, using a rat model of a peripheral nerve injury (PNI) and in vitro model established by RSC96 cells treated with tert-butyl hydroperoxide (TBHP), we found that Parkin-mediated mitophagy can effectively reduce the production of mitochondrial reactive oxygen species (ROS), maintain the balance of mitochondrial membrane potential, maintain autophagic flux, and inhibit mitochondrial apoptosis. At the same time, we found that the increase of Parkin under stress is a manifestation of the RSC96 cells' resistance to oxidative stress to maintain RSC96 cells' balance. In our experiment, melatonin is similar to a Parkin agonist, up-regulating the expression of Parkin, enhancing all the positive results of Parkin in a stress state, such as inhibiting active oxygen production, maintaining autophagic flux, and inhibiting mitochondrial apoptosis. In addition, we design in vivo experiments to verify in In vitro experiments. In in vivo, melatonin promotes the expression of Parkin, maintains autophagic flux, inhibits apoptosis, promotes myelin regeneration, reduces the regeneration of collagen fibers around damaged tissues, and promotes peripheral nerve repair. When adenovirus was used to down-regulate the expression of Parkin, we found that all the positive effects of melatonin were attenuated. Collectively, these findings indicate that melatonin upregulates Parkin-mediated mitophagy and promotes peripheral nerve repair. The results provide a basis for development of effective drugs for PNI treatment.

Exploring the Correlation Between the Regulation of Macrophages by Regulatory T Cells and Peripheral Neuropathic Pain.

OBJECTIVE: Intractable pain after peripheral nerve injury has become a major concern in the field of pain. Current evidence shows that routine medications or surgical treatment is associated with inconsistent results and different curative effects. Stable and effective treatment methods in clinical practice are also lacking. To date, there is no consensus on the pathophysiological mechanisms of pain. The present study investigates the potential regulatory role of regulatory T cells in the differentiation of macrophages on dorsal root ganglion (DRG) and explores the mechanism of nociceptive signals in the signal transfer station. The findings are expected to guide the prevention of various types of peripheral neuropathic pain. METHODS: Thirty-six male Sprague Dawley (SD) rats and 18 male Nude rats, of equal weight (250-300g), were used in this study. The rats were divided into 3 groups: SD rat sciatic nerve transection group (SNT group, n = 18), SD rat nerve transection experimental group (SNT/RAPA group, n = 18) and Nude rat nerve transection experimental group (SNT/NUDE group, n = 18). The behavior related to neuropathic pain of animals were comprehensively evaluated in all groups. Furthermore, we analyzed the degree of neuroma development, histology, gene, and protein expression, and compared their correlation with the ultrastructural changes of M1/M2 type differentiation of macrophages in DRG. RESULTS: Sciatic nerve transection (SNT), induced the aggregation of several types of macrophages in lumbar DRG of SD rats leading to a higher ratio of M1/M2. Following the inhibition of the M1 type polarization of macrophages, axon outgrowth increased significantly. A significantly lower average autotomy score was reported in the SNT/NUDE group (*p < 0.05) and the SNT/RAPA group (@ p < 0.05) as compared to that of the SNT group. The SNT/NUDE group showed no noticeable neuroma formation 30 days after the nerve transection. However, bulbous neuromas were observed in the nerve stumps of both the SNT control and SNT/RAPA groups. Immunofluorescence staining revealed a significant decrease in the proportion of M1/M2 macrophages in lumbar DRG of the SNT/NUDE group (** p < 0.001) and the SNT/RAPA group (@ p < 0.05) compared to the SNT group. The expression of pain-related proteins was also decreased (@ p < 0.05, *p < 0.05,** p < 0.001). Also, the expression of alpha-smooth muscle actin (α-SMA), neurofilament 200 (NF-200), and nerve growth factor low-affinity receptor p75 were significantly down-regulated in the nerve tissue (@ p < 0.05, @@ p < 0.001, ** p < 0.001). CONCLUSION: M1/M2 type differentiation of macrophages on DRG plays a significant role in the formation of traumatic painful neuroma after neurotomy. In combination with our previous study, the results of this study suggest that regulatory T cells reduce the ratio of M1/M2 macrophages and alleviate the pain of neuroma by regulating the polarization direction of macrophages on neuroma. These findings provide key insights into developing new strategies to manage painful neuroma.

A new insight on peripheral nerve repair: the technique of internal nerve splinting.

OBJECTIVE: Neuropathic pain produced by symptomatic neuromas is an important problem after peripheral nerve injury (PNI). End-to-end anastomosis of the nerve stump for PNI is well established but cannot efficiently prevent neuroma-in-continuity formation. METHODS: Sciatic nerve injury was used in the experimental model. Seventy-two rats were randomly divided into four groups: rats with nerve anastomosis sites supported with silicone tubes represented the internal nerve splinting (INS) group (n = 18); rats with end-to-end nerve anastomosis represented control group 1 (CON1) (n = 18); rats with INS and the nerve anastomosis site represented control group 2 (CON2) (n = 18); and rats that underwent the same surgical procedures for skin and muscle operations but without sciatic nerve injury represented the normal group (n = 18). RESULTS: Gross evaluations of the nerve anastomosis sites, gastrocnemius muscle atrophy, axonal regeneration and remyelination, neuropathic pain, and scar hyperplasia of the neuromas were performed, as well as motor function evaluations. Axonal regeneration, remyelination, and gastrocnemius muscle atrophy were similar between the INS group and CON1 (p > 0.05). However, neuropathic pain and scar hyperplasia-as evaluated according to the expression of anti-sigma-1 receptor antibody and anti-α-smooth muscle actin, respectively-and the weight ratios of the neuromas were reduced in the INS group compared with those of CON1 and CON2 (p < 0.05). CONCLUSIONS: Application of INS in nerve repair effectively prevented traumatic neuroma-in-continuity formation and inhibited neuropathic pain without influencing nerve regeneration in rats.

Augmenting Peripheral Nerve Regeneration with Adipose-Derived Stem Cells.

Peripheral nerve injuries (PNIs) are common and debilitating, cause significant health care costs for society, and rely predominately on autografts, which necessitate grafting a nerve section non-locally to repair the nerve injury. One possible approach to improving treatment is bolstering endogenous regenerative mechanisms or bioengineering new nervous tissue in the peripheral nervous system. In this review, we discuss critical-sized nerve gaps and nerve regeneration in rats, and summarize the roles of adipose-derived stem cells (ADSCs) in the treatment of PNIs. Several regenerative treatment modalities for PNI are described: ADSCs differentiating into Schwann cells (SCs), ADSCs secreting growth factors to promote peripheral nerve growth, ADSCs promoting myelination growth, and ADSCs treatments with scaffolds. ADSCs' roles in regenerative treatment and features are compared to mesenchymal stem cells, and the administration routes, cell dosages, and cell fates are discussed. ADSCs secrete neurotrophic factors and exosomes and can differentiate into Schwann cell-like cells (SCLCs) that share features with naturally occurring SCs, including the ability to promote nerve regeneration in the PNS. Future clinical applications are also discussed.

Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury.

Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.

Aligned nanofiber nerve conduits inhibit alpha smooth muscle actin expression and collagen proliferation by suppressing TGF-ß1/SMAD signaling in traumatic neuromas.

Transforming growth factor-beta 1 (TGF-ß1) is a powerful activator of connective tissue synthesis that is strongly associated with the pathophysiology of traumatic neuroma. Previous studies have demonstrated that aligned nanofiber conduits made from silk fibroin and poly (L-lactic acid-co-ε-caprolactone; PLCL) could prevent traumatic neuromas. In the present study, the possible mechanisms of conduits in treating traumatic neuromas were investigated to provide theoretical basis for procedures. Aligned nanofiber conduits were used for nerve capping. Sciatic nerves of Sprague-Dawley rats were used to create an animal model. The present study contains two parts, each including four experimental groups. SB-431542/SRI-011381 hydrochloride was used to suppress/enhance TGF-ß1/SMAD signaling. Part I discussed the connections between traumatic neuroma and the proliferation of alpha smooth muscle actin (α-SMA) and collagen; it also investigated the therapeutic effect of conduits. Part II hypothesized that conduits suppressed TGF-ß1/SMAD signaling. Histological characteristics, quantitative analysis of α-SMA, collagens and signaling-related parameters were assessed and compared among groups one month postoperatively. Results from Part I demonstrated that aligned nanofiber conduits suppressed the expression of α-SMA and collagens; and results from Part II revealed the downregulation of pathway-related proteins, suggesting that the suppression was mediated by TGF-ß1/SMAD signaling. Aligned nanofiber conduits may be effective nerve capping biomaterials. One of the mechanisms involves suppressing TGF-ß1/SMAD signaling. Novel treatments using aligned nanofiber conduits could be developed to manage traumatic neuromas.

The feasibility and survival mechanism of a large free flap supported by a novel hybrid perfusion mode.

OBJECTIVES: In this study, we presented a novel hybrid perfusion mode in an attempt to provide a new strategy to improve the survival of an extended large flap and discuss its possible mechanisms. MATERIALS AND METHODS: A 14 × 10 cm flap was designed on the rabbit abdomen. Ninety-six rabbits were randomly divided into three groups based on the flap perfusion mode: control group I (CON 1, physiological perfusion mode with bilateral deep inferior epigastric vascular pedicles intact), control group II (CON 2, physiological perfusion mode with single deep inferior epigastric vascular pedicle intact), hybrid nourished group (physiological perfusion as in CON 2 combined with arterialized venous nonphysiological perfusion mode, referred to as a hybrid perfusion mode). Flap survival, status of vascular perfusion, microvasculature, histopathology, expression of CD34, eNOs, VEGF and metabolic status of the flaps by LC-MS were assessed in each group. RESULTS: The results of "hybrid nourished" flaps were similar to the traditional flaps in terms of flap survival, level of vascular perfusion and microvasculature except the status of metabolites. CONCLUSIONS: The feasibility of this novel hybrid perfusion mode will greatly extend the indications of flap transfer and efficiently improve the survival reliability of large flaps. In a sense, this mode will be an ideological emancipation for the field of flap surgery.

Risk Factors Associated With Postoperative Recurrence in Patients With Tenosynovial Giant Cell Tumor of the Hand: A Retrospective Cohort Study.

Identification of risk factors for recurrence of tenosynovial giant cell tumors of the hand is crucial to provide adequate preoperative counseling and tailor surgical treatment. However, the risk factors are still controversial, which are the subject of this research.Recently, we conducted a retrospective cohort study of 135 consecutive patients with giant cell tumors of the tendon sheath of the hand from January 2010 to July 2016. All patients underwent surgical excision, received necessary imaging examinations, and had routine follow-up and thus were identified as those who had recurrence by confirmation of reoperation, and the duration ranged from 24 to 103 months (mean, 53.5 ± 21.4 months). There were 14 local recurrences (10.4%) within 6 to 24 months, respectively, after surgery. Data pertaining to sex, age, tumor sites, tumor size, tumor number, course of disease, bone erosion, tumor growth patterns, anesthesia mode, and the surgeon's experience were all extracted, and Cox regression models were used to estimate recurrence rate with adjustment for potential confounders.According to the Cox regression analysis, the recurrence rate after surgery was significantly higher in patients with a diffused form than in those with a localized one (P = 0.001); in addition, patients with 2 or more tumors had a much higher postoperative recurrence rate than did those with only 1 tumor (P = 0.023).This study suggested that the recurrence rate of tenosynovial giant cell tumors of the hand was closely related to the tumor number and tumor growth patterns.

An aligned nanofiber nerve conduit that inhibits painful traumatic neuroma formation through regulation of the RhoA/ROCK signaling pathway.

OBJECTIVE: Traumatic neuromas represent a prevalent source of neuropathic pain. As of yet, there has been no single treatment method that can guarantee permanent relief of symptoms. Although nerve-capping techniques have shown promise, their exact mechanisms remain elusive. The authors' aim was to examine the role of the RhoA/ROCK signaling pathway in the prevention of neuroma formation after neurectomy utilizing a nerve-capping technique. METHODS: An aligned nanofiber tube was fabricated to cap the sciatic nerve in Sprague Dawley rats. The rats (n = 60) were randomly divided into the aligned SF/P (LLA-CL) capping group (capping group, n = 20), the capping and Y-27632 (ROCK pathway inhibitor) intervention group (intervention group, n = 20), and the no-capping group (control group, n = 20). The authors undertook a comprehensive assessment of the capping group, examining the animals' behavior, the extent of neuroma development, histology, gene and protein expression, and ultrastructural changes associated with the RhoA/ROCK signaling pathway. These findings were compared with those in the intervention and control groups. RESULTS: The inciting injury resulted in the expression of the RhoA/ROCK signaling pathway, as well as its further upregulation in peripheral neurons. Axon outgrowth was significantly increased when RhoA/ROCK signaling pathway was suppressed. The average autotomy score in the capping group was observed to be much lower than that of the intervention and control groups. At 30 days postneurectomy, the capping group displayed no obvious neuroma formation, while a bulbous neuroma was found in the nerve stumps of both the control and intervention groups. Quantitative real-time polymerase chain reaction and the Western blot analysis demonstrated that the expression of myelin-associated glycoprotein was substantially upregulated in the capping group; in contrast, the expression of NF-200 was significantly downregulated. The expression of myosin light chain was notably lower in the intervention group, but there was no significant difference when compared with the control group (p > 0.05). CONCLUSIONS: The RhoA/ROCK signaling pathway has emerged as a critical player in the process of traumatic neuroma formation after neurectomy. It is possible that the nerve-capping technique could generate a "regenerative brake" based on the regulation of the RhoA/ROCK signaling pathway in this event. These findings may provide concrete evidence that could help develop new strategies for the management of painful neuromas.

The effect of chemical hemodynamic regulation on the survival of arterialized venous flaps.

The role of nitric oxide (NO) on the microcirculation of arterialized venous flaps (AVFs) remains controversial. We aimed to investigate the effect of hemodynamic regulation using nitric oxide synthase (NOS) inhibitor and its agonist as a chemical intervention on the survival of AVF. A 10 × 8 cm arterialized venous flap was designed symmetrically on the rabbit abdomen. Thirty-six rabbits were used and randomly divided into three groups: control group, L-arg group and L-NAME group, respectively. The L-arg group and the L-NAME group received intraperitoneal injections of L-arginine (a NOS agonist, 1 g/kg/d) and L-NAME (nitro-L-arginine-methyl ester, a NOS inhibitor, 50 mg/kg/d) respectively, whereas the control group received intraperitoneal injections of the same amount of saline. Flap viability, water content, status of vascular perfusion and gene expression of eNOS and HIF-1α in each group were observed and analyzed. The average value of water content (venous congestion) in the L-arg group was the highest in comparison with the control group and the L-NAME group with a statistically significant difference (all p < .001). Similar results regarding blood perfusion state, gene expression of eNOS and HIF-1α and flap survival status were found among the three groups. The early application of L- NAME as a chemical hemodynamic intervention could stop the cascade of flap swelling, congestion and necrosis due to overexpression of NO and be beneficial to the AVF survival. Our findings may develop a new strategy as a solution for the inconsistent survival of AVFs.

Treatment of Intraosseous Ganglion Cyst of the Lunate: A Systematic Review.

PURPOSE: Intraosseous ganglion cyst (IGC) is a rare disease, particularly in lunate. The objective of this study was to summarize current knowledge on the treatment of IGC of the lunate, through a literature review, to provide a therapeutic strategy for this rare disease. METHODS: The PubMed, ISI Web of Science, Cochrane Library, EMBASE, Science Direct database were searched with a set of predefined inclusion and exclusion criteria. Manual searches for references were performed to find potential relevant studies. The authors extracted data from the articles selected. RESULTS: Different treatment modalities of IGC of the lunate were described, all of which were divided into 3 categories: conservative treatment, classical surgical procedures, and novel surgical procedures. An overview on the main treatment modalities for IGC of the lunate was provided. CONCLUSIONS: Conservative treatments can be the doctors' first choice for patients with IGC. Surgical procedure is advised when conservative treatment fails. Traditional surgical curettage with autologous bone grafting is the mainstay of treatment with satisfactory outcomes; however, novel surgical techniques like arthroscopically assisted minimally invasive technique or filling with bone cement are considered as more promising attempts with less trauma and shorter recovery period. Nonetheless, studies with high levels of evidence are guaranteed for developing widely accepted clinical treatment guidelines.

Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation.

Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Autophagy is involved in the development and/or progression of many diseases, including neuropathic pain. Emerging evidence suggests that metformin relieves neuropathic pain in several neuropathic pain models; however, metformin's cellular and molecular mechanism for pain relief remains unknown. In this study, we investigated the therapeutic effects of metformin on pain relief after spinal nerve ligation (SNL) and its underlying mechanism of autophagy regulation. Behavioural analysis, histological assessment, expression of c-Fos and molecular biological changes, as well as ultrastructural features, were investigated. Our findings showed that the number of autophagosomes and expression of autophagy markers, such as LC3 and beclin1, were increased, while the autophagy substrate protein p62, as well as the ubiquitinated proteins, were accumulated in the ipsilateral spinal cord. However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and analgesic effects of metformin on SNL. Taken together, these results illustrated that metformin relieved neuropathic pain through autophagy flux stimulation and provided a new direction for metformin drug development to treat neuropathic pain.

Individual Treatment of Delayed Distal Biceps Tendon Rupture: Case Report and Literature Review.

INTRODUCTION: Complicated elbow injuries (elbow injuries with bone and soft tissue injury) with distal biceps tendon ruptures (DBTRs) are not uncommon. There are several treatment modalities in different situations of injuries. In this article, we reported 3 successful individual treatments of delayed DBTR with complicated elbow injuries. MATERIALS AND METHODS: Three cases of complicated elbow injuries treated between 2010 and 2016 were reviewed. The delayed DBTR cases were summarized and treated. Mayo Elbow Performance Score value, range of motion, and visual analog scale score were used to assess outcomes after a minimum follow-up of 12 months. RESULTS: All 3 patients were male, aged 47 to 54 years (mean, 49.6 years). Patients received surgical treatments. After a mean follow-up of 13.7 months, in cases 1 and 2, Mayo Elbow Performance Score values improved by 50% and 100%, elbow flexion-extension arc were 115 degrees and 110 degrees, pronation-supination arc were 130 degrees and 120 degrees. Arthrodesis case reported pain relief; visual analog scale score for pain was 0 to 1. No postoperative complications were observed, and all patients were satisfied with the results. CONCLUSIONS: Individual treatment is advised in DBTR with complicated elbow injuries. Secondary treatment of DBTR can achieve satisfactory results using individual strategies depending on patients' overall condition.

Effects of Hydrogel-Fiber on Cystic Cavity after Spinal Cord Injury.

Spinal cord injury (SCI) affects millions of people around the world, however, functional recovery is far from satisfying. The continuous emergence of biomaterials provides a new idea for the repair of SCI. Hydrogels can mimic the extracellular matrix (ECM), however, the unstable hydrogel shape limits its application. In this study, we evaluate the effect of hydrogel fiber (Polycaprolactone, PCL fiber was added to the hydrogel) on the recovery after SCI. 20 adult male Wistar rats were randomly divided into 4 groups: SCI+hydrogel group (H), SCI+hydrogel + PCL fiber group (HF), SCI group (SCI) and SHAM group (SHAM) and (N=5). SCI contusion injury was induced by a MASCIS Impactor (20g weight, 50cm high) at the T9 level in rats. Hydrogels or PCL fiber were administered into the SCI site one week after surgery. Periodical Basso, Beattie, and Bresnahan (BBB) locomotor score, spinal cord hematoxylin and eosin stain (HE) staining, and immunofluorescence staining were performed 28 days after the operation. HE staining showed that the average cystic cavity area in SCI (20.78 ±2.93 mm2) group was significantly higher than that in H group (6.54 ±0.85 mm2), HF group (5.06 ±0.76 mm2) and SHAM group (1.76 ±0.27 mm2) (P <; 0.001). There was no significant difference in BBB motor score among the HF group (16.80±1.10), SCI (14.20±1.09) and H group (15.00±1.23) (P > 0.05), except the sham group. Immunofluorescence showed higher NeuN positive cells in both the H group and the HF group. This preliminary result may indicate that PCL fiber optimized the strength of hydrogels, thus providing better support for the axon regeneration. Future investigation is needed to further characterize PCL fiber and elucidate related mechanisms.

Treatment of osteoarthritis of the elbow with open or arthroscopic debridement: a narrative review.

BACKGROUND: Elbow osteoarthritis (OA) is a common disabling condition because of pain and loss of motion. Open and arthroscopic debridement are the preferred treatment, however there is no consensus on which treatment modality is suited to which category of patient or stage of disease. The objective of this study was to narratively review the literature for a more comprehensive understanding of its treatment options and associated outcomes, trying to provide a better treatment plan. METHODS: The PubMed database, EMBASE, Cochrane Library, and Google Scholar were searched, using the keywords (elbow [title/abstract] and osteoarthritis [title/abstract] and (surgery or open or arthroscop* or debridement or ulnohumeral arthroplasty) including all possible studies with a set of inclusion and exclusion criteria. RESULTS: A total of 229 studies were identified. Twenty-one articles published between 1994 and 2016 satisfied the inclusion and exclusion criteria including 651 elbows in 639 patients. After comparison, mean postoperative improvement in (ROM) was 28.6° and 23.3°,Mayo elbow performance score/index(MEPS/MEPI) 31 and 26.8 and the total complication rate was 37(11.5%), and 18(5.5%) for open and arthroscopic procedure. CONCLUSIONS: This narrative review could not provide an insight on which surgical procedure is superior to the other due to the poor orthopedics literature. However, from the data we obtained the open and arthroscopic debridement procedures seem to be safe and effective in the treatment of elbow OA. The optimal surgical intervention for the treatment of symptomatic elbow OA should be determined depending on patients' conditions.

Debridement arthroplasty of a rare case of elbow stiffness. A case report and literature review.

INTRODUCTION: Elbow stiffness is a common condition that affects the quality of life of patients. Melorheostosis of the elbow associated with elbow stiffness is extremely rare. PRESENTATION OF CASE: We report the case of a 28 yr old male who presented with elbow stiffness which occurred within one year without prior history of trauma or infection. The patient had decrease in range of motion together with progressive worsening pain that forced him to seek medical attention. DISCUSSION: There is no standard treatment for melorheostosis, and management plans must be made on an individual patient basis. The aims of treatment are pain relief and maintaining function. CONCLUSION: Debridement arthroplasty is safe and effective in treating elbow stiffness associated with Melorheostosis.