Plasma exosomes improve peripheral neuropathy via miR-20b-3p/Stat3 in type I diabetic rats.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and the main cause of non-traumatic amputation, with no ideal treatment. Multiple cell-derived exosomes have been reported to improve the progression of DPN. Blood therapy is thought to have a powerful repairing effect. However, whether it could also improve DPN remains unclear. RESULTS: In this study, we found that microRNA (miRNA) expression in plasma-derived exosomes of healthy rats (hplasma-exos) was significantly different from that of age-matched DPN rats. By injection of hplasma-exos into DPN rats, the mechanical sensitivity of DPN rats was decreased, the thermal sensitivity and motor ability were increased, and the nerve conduction speed was accelerated. Histological analysis showed myelin regeneration of the sciatic nerve, increased intraepidermal nerve fibers, distal local blood perfusion, and enhanced neuromuscular junction and muscle spindle innervation after hplasma-exos administration. Compared with plasma exosomes in DPN, miR-20b-3p was specifically enriched in exosomes of healthy plasma and was found to be re-upregulated in the sciatic nerve of DPN rats after hplasma-exos treatment. Moreover, miR-20b-3p agomir improved DPN symptoms to a level similar to hplasma-exos, both of which also alleviated autophagy impairment induced by high glucose in Schwann cells. Mechanistic studies found that miR-20b-3p targeted Stat3 and consequently reduced the amount of p-Stat3, which then negatively regulated autophagy processes and contributed to DPN improvement. CONCLUSIONS: This study demonstrated that miRNA of plasma exosomes was different between DPN and age-matched healthy rats. MiR-20b-3p was enriched in hplasma-exos, and both of them could alleviated DPN symptoms. MiR-20b-3p regulated autophagy of Schwann cells in pathological states by targeting Stat3 and thereby inhibited the progression of DPN.

Application of stem cells combined with biomaterial in the treatment of intervertebral disc degeneration.

As the world population is aging, intervertebral disc degeneration (IDD) is becoming a global health issue of increasing concern. A variety of disc degeneration diseases (DDDs) have been proven to be associated with IDD, and these illnesses have significant adverse effects on both individuals and society. The application of stem cells in regenerative medicine, such as blood and circulation, has been demonstrated by numerous studies. Similarly, stem cells have made exciting progress in the treatment of IDD. However, due to complex anatomical structures and functional requirements, traditional stem cell injection makes it difficult to meet people's expectations. With the continuous development of tissue engineering and biomaterials, stem cell combined with biomaterials has far more prospects than before. This review aims to objectively and comprehensively summarize the development of stem cells combined with contemporary biomaterials and the difficulties that need to be overcome.

Rapid Spontaneous Total Fusion of Neuropathic Arthropathy of the Wrist After Limited Intercarpal Arthrodesis: A Case Report and Brief Literature Review.

Background: Previous reports on the treatment of neuropathic arthropathy of the wrist were generally conservative, with few case reports of treatment with osteoarticular surgery. Case Presentation: A 25-year-old right-handed male complained of unpainful swelling of the dorsal aspect of his right wrist for 3 years. He was at that time diagnosed with synovitis and radiocarpal arthritis. The patient underwent a partial Four-Corner Arthrodesis and Synoviectomy to preserve motor function. Over the next 2 months, his right wrist also developed painful redness, with progressive swelling and stiffness. Rheumatoid arthritis, tuberculosis arthritis, and infectious diseases were ruled out in this case. Magnetic resonance imaging (MRI) indicated that he had Chiari II syringomyelia so the patient was eventually diagnosed with destructive neuropathic arthropathy (syringomyelia). After 2 months of conservative treatment, the patient's right wrist spontaneously and completely fused and the pain disappeared. Conclusion: Neuropathic arthropathy of the wrist is a rare but clinically significant disease due to its effect on the function of the active limb. Surgeons should rule out a diagnosis of it when treating patients with wrist swelling and osteoarticular abnormalities, otherwise, limited intercarpal arthrodesis should not be taken as a treatment option. Inappropriate partial surgery is likely to lead to rapid total fusion of neuropathic arthropathy of the wrist.

The free flap based on a single proximal perforator of the radial artery: ultrasonography study and clinical applications in reconstruction of soft tissue defects in finger.

OBJECTIVES: To locate an anastomosable constant perforator of the radial artery on the proximal forearm using ultrasonography and describe the application of a free radial artery flap based on a single proximal perforator for the reconstruction of soft tissue defects in finger. METHODS: In 20 forearms (ten right and ten left) from ten volunteers, the perforators in the proximal half of the forearm from the radial artery were visualized using ultrasonography. The free radial artery perforator flaps based on the single perforator were used to reconstruct digital soft tissue defects in four cases between October 2017 and May 2018. RESULTS: Of the 20 forearms, an anastomosable perforator was consistently detected in the radial artery in the forearm's proximal half. The perforator diameter was 0.7 ± 0.1 mm, and the pedicle length was 12 ± 3 mm according to ultrasonography. The perforator's location was far from the elbow crease (8.8 ± 1.4 cm), and the relative distance of the perforator's location from the elbow crease to the wrist crease was 37.2% ± 4.8%. In clinical cases, all flaps survived. Flap size ranged from 3.5 to 6.5 cm in length and 2.3-3.0 cm in width. Donor sites of the forearm were closed primarily in all cases. During a mean period of 12 months (8-14 months) follow-up, the average static 2-PD was 13.8 mm (10-18 mm) in the flap area, and the ROM of DIP was 35° (30-40°), PIP was 82° (45-110°), and MP was 85° (70-90°) of the affected finger. The mean Brief Michigan Hand Questionnaire (BMHQ) score was 72.9 (60.4-85.4) in the affected hand. CONCLUSIONS: An anastomosable perforator is consistently located on the radial artery in the proximal half of the forearm. The free radial artery flap based on this single perforator provides acceptable functional and cosmetic outcomes for reconstructing digital soft tissue defects. With the preservation of the forearm's main vessel (radial artery), this flap provides another reliable option for hand surgeons to reconstruct small soft tissue defects in finger.

Protein Tyrosine Phosphatase Receptor Type D Regulates Neuropathic Pain After Nerve Injury via the STING-IFN-I Pathway.

Neuropathic pain is usually caused by injury or dysfunction of the somatosensory system, and medicine is a common way of treatment. Currently, there are still no satisfactory drugs, like opioids and lidocaine, which carry a high risk of addiction. Protein tyrosine phosphatase receptor type D (PTPRD) is a known therapeutic target in addiction pathways and small molecule inhibitors targeting it, such as 7-butoxy illudalic acid analog (7-BIA), have recently been developed to tackle addition. PTPRD is also upregulated in the dorsal root ganglion (DRG) in a rat model of neuropathic pain, but is not yet clear whether PTPRD contributes to the development of neuropathic pain. Here, we established a chronic constriction injury (CCI) and evaluated PTPRD expression and its association with neuropathic pain. PTPRD expression was found to gradually increase after CCI in DRGs, and its expression was concomitant with the progressive development of hypersensitivity as assessed by both mechanical and thermal stimuli. Both PTPRD knockdown and administration of PTPRD inhibitor 7-BIA alleviated CCI-induced neuropathic pain while upregulating STING and IFN-α in the DRG. Treatment with H-151, a STING inhibitor, abolished the analgesic effects of PTPRD knockdown. Taken together, our study suggests that increased levels of PTPRD in the DRG following CCI are involved in the development of neuropathic pain via the STING-IFN-I pathway. 7-BIA, a small molecule inhibitor of PTPRD with anti-addiction effects, may represent a novel and safe therapeutic strategy for the clinical management of neuropathic pain without the risk of addiction.

Erratum: "miR-182 promotes cell proliferation and invasion by inhibiting APC in melanoma".

[This corrects the article on p. 1900 in vol. 11, PMID: 31938296.].

Deep Inferior Epigastric Flap Combined Bilateral-Anterolateral Thigh Flap for the Coverage of Both Lower Extremity Soft-Tissue Defect: A Case Report and a Literature Review.

BACKGROUND/PURPOSE: Anterolateral thigh perforator (ALTP) flap and deep inferior epigastric perforator (DIEP) flap have been advantageous over traditional myocutaneous flaps as they preserve the integrity of donor site muscles and minimize the damage and complication to donor site structures. Here, we reported the efficacy of free ALTP and DIEP in the repair of large skin area and soft tissue defects on both lower limbs after trauma. CASE REPORT: A 19-year-old female traffic accident victim presented with multiple open bilateral fractures to the lower extremities with joint dislocation, massive skin and soft tissue defects, and multiple soft tissue contusion. Wounds on both lower extremities were covered with VSD (Vacuum Sealing Drainage). The tibiofibular and ankle joints on both lower limbs were fixed using external fixators. DIEP and ALTP flap were performed at different times. RESULTS: After transfer, the vascular pedicle was anastomosed to the anterior tibial artery, posterior tibial artery, and the accompanying vein. After the operation, the donor site was directly closed and sutured. All flaps survived with a good appearance, leaving only a linear scar at the donor site. CONCLUSION: This case shows that free ALTP and DIEP flaps are ideal for repairing large skin area and soft tissue defects in bilateral lower limbs after trauma.

α-MSH-PE38KDEL Kills Melanoma Cells via Modulating Erk1/2/MITF/TYR Signaling in an MC1R-Dependent Manner.

BACKGROUND/OBJECTIVE: The immunotoxin α-MSH-PE38KDEL consisting of α-MSH and PE38KDEL showed high cytotoxicity on MSH receptor-positive melanoma cells, suggesting that α-MSH-PE38KDEL might be a potent drug for the treatment of melanoma. Herein, we explored whether the Erk1/2/MITF/TYR signaling, a verified target of α-MSH/MC1R, was involved in α-MSH-PE38KDEL-mediated cytotoxicity. METHODS: Human melanoma cell line A375, mouse melanoma cell line B16-F10, human breast cancer cell line MDA-MB-231 and human primary epidermal melanocytes (HEMa) with different expression levels of MC1R were used in this study. Cell apoptosis and viability were determined by using flow cytometry and MTT assays. Protein expressions were tested by Western blotting. RESULTS: The expression levels of MC1R in A375 and B16-F10 cells were significantly higher than that of MDA-MB-231 and HEMa. α-MSH-PE38KDEL treatment induced a significant inhibition in cell viability in A375 and B16-F10 cells, while showed no obvious influence in the viability of MDA-MB-231 and HEMa cells. However, knockdown of MC1R abolished α-MSH-PE38KDEL role in promoting cell apoptosis in A375 and B16-F10 cells, and upregulation of MC1R endowed α-MSH-PE38KDEL function to promote cell apoptosis in MDA-MB-231 and HEMa cells. Additionally, α-MSH-PE38KDEL treatment increased the phosphorylation levels of Erk1/2 and MITF (S73), and decreased MITF and TYR expressions in an MC1R-dependent manner. All of the treatments, including inhibition of Erk1/2 with PD98059, MC1R downregulation and MITF overexpression weakened the anti-tumor role of α-MSH-PE38KDEL in melanoma. CONCLUSION: Collectively, this study indicates that α-MSH-PE38KDEL promotes melanoma cell apoptosis via modulating Erk1/2/MITF/TYR signaling in an MC1R-dependent manner.

A novel risk score model based on eight genes and a nomogram for predicting overall survival of patients with osteosarcoma.

BACKGROUND: This study aims to identify a predictive model to predict survival outcomes of osteosarcoma (OS) patients. METHODS: A RNA sequencing dataset (the training set) and a microarray dataset (the validation set) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. Differentially expressed genes (DEGs) between metastatic and non-metastatic OS samples were identified in training set. Prognosis-related DEGs were screened and optimized by support vector machine (SVM) recursive feature elimination. A SVM classifier was built to classify metastatic and non-metastatic OS samples. Independent prognosic genes were extracted by multivariate regression analysis to build a risk score model followed by performance evaluation in two datasets by Kaplan-Meier (KM) analysis. Independent clinical prognostic indicators were identified followed by nomogram analysis. Finally, functional analyses of survival-related genes were conducted. RESULT: Totally, 345 DEGs and 45 prognosis-related genes were screened. A SVM classifier could distinguish metastatic and non-metastatic OS samples. An eight-gene signature was an independent prognostic marker and used for constructing a risk score model. The risk score model could separate OS samples into high and low risk groups in two datasets (training set: log-rank p < 0.01, C-index = 0.805; validation set: log-rank p < 0.01, C-index = 0.797). Tumor metastasis and RS model status were independent prognostic factors and nomogram model exhibited accurate survival prediction for OS. Additionally, functional analyses of survival-related genes indicated they were closely associated with immune responses and cytokine-cytokine receptor interaction pathway. CONCLUSION: An eight-gene predictive model and nomogram were developed to predict OS prognosis.

Bilateral radial collateral ligament rupture in a shoemaker: A case report and brief literature review.

INTRODUCTION: Rupture of the radial collateral ligament (RCL) of the index metacarpophalangeal (MCP) joint is mostly related to acute local mechanical causes, which severely affect the stability of the MCP joint. However, few cases of chronic bilateral job-related RCL injury have been reported in the literature. There is no consensus on the knowledge of the disease to date. Here, we present an extremely rare case of chronic bilateral RCL injury. PATIENT CONCERNS: A 58-year-old female shoemaker presented with chief complaints of swelling and pain in the radial aspect of the MCP joint of bilateral index fingers since 2 years. There was no history of acute RCL injury. The persistent pain was aggravated while gripping, pulling, buttoning, and twisting. DIAGNOSIS: Based on the combination of physical examination, X-ray, and ultrasonic and magnetic resonance imaging, the patient was diagnosed with bilateral tear of the RCLs and joint dislocation of the index MCP joint. Eventually, intra-operative findings confirmed the diagnosis. INTERVENTION: The patient underwent bilateral index MCP joint fusion followed by immobilization for 6 weeks. Functional therapy was started after immobilization. OUTCOMES: The patient's chief complaints were significantly alleviated after the operation. At the 12-month follow-up, the patient returned to a full level of activity as a shoemaker without any complications. CONCLUSION: Compared to acute RCL rupture of the index MCP joint, occupation may play an important role in the diagnosis of chronic RCL rupture of the index MCP joint. Our report will provide more diagnostic and treatment experience to deal with this type of injury.

Open versus endoscopic carpal tunnel release: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) both have advantages and disadvantages for the treatment of carpal tunnel syndrome (CTS). We compared the effectiveness and safety of ECTR and OCTR based on evidence from a high-level randomized controlled trial. METHODS: We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Medline to identify relevant articles published until August 2019. Data regarding operative time, grip strength, Boston Carpal Tunnel Questionnaire scores, digital sensation, patient satisfaction, key pinch strength, return to work time, and complications were extracted and compared. All mean differences (MD) and odds ratios (OR) were expressed as ECTR relative to OCTR. RESULTS: Our meta-analysis contained twenty-eight studies. ECTR was associated with significantly higher satisfaction rates (MD, 3.13; 95% confidence interval [CI], 1.43 to 4.82; P = 0.0003), greater key pinch strengths (MD, 0.79 kg; 95% CI, 0.27 to 1.32; P = 0.003), earlier return to work times (MD, - 7.25 days; 95% CI, - 14.31 to - 0.19; P = 0.04), higher transient nerve injury rates (OR, 4.87; 95% CI, 1.37 to 17.25; P = 0.01), and a lower incidence of scar-related complications (OR, 0.20; 95% CI, 0.07 to 0.59; P = 0.004). The permanent nerve injury showed no significant differences between the two methods (OR, 1.93; 95% CI, 0.58 to 6.40; P = 0.28). CONCLUSIONS: Overall, evidence from randomized controlled trials indicates that ECTR results in better recovery of daily life functions compared to OCTR, as revealed by higher satisfaction rates, greater key pinch strengths, earlier return to work times, and fewer scar-related complications. Our findings suggest that patients with CTS can be effectively managed with ECTR.

Long non-coding RNA MALAT1 promotes the proliferation and migration of Schwann cells by elevating BDNF through sponging miR-129-5p.

The proliferation and migration of Schwann cells contribute to nerve regeneration after peripheral nerve injury (PNI). In recent years, roles of long non-coding RNAs (lncRNAs) in PNI have been gradually uncovered. However, a highly conserved nuclear lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in peripheral nerve regeneration remains enigmatic. MALAT1 expression in injured sciatic nerve of mice with PNI was measured by real-time PCR. The proliferative and migrative abilities of Schwann cells were determined after upregulating or downregulating Malat1. The relationship among MALAT1, miR-129-5p, and BDNF was measured. In this study, we found elevated MALAT1 expression in injured sciatic nerve. MALAT1 upregulation in Schwann cells promoted cell proliferation and migration. However, downregulation of MALAT1 caused the suppression of Schwann cell proliferation and migration. Mechanistically, we discovered MALAT1 negatively regulated miR-129-5p through directly binding. Brain-derived neurotrophic factor (BDNF) was a target of miR-129-5p. MALAT1 positively modulated BDNF expression and secretion via decreasing miR-129-5p. Downregulation of BDNF rescued the influences of MALAT1 overexpression on Schwann cell proliferation and migration. In conclusion, MALAT1 was enhanced after PNI and it promoted the proliferation and migration of Schwann cells through sponging miR-129-5p to increase BDNF expression and secretion. This study proved that MALAT1 may be a vital regulator in peripheral nerve regeneration.

Oleanolic acid administration alleviates neuropathic pain after a peripheral nerve injury by regulating microglia polarization-mediated neuroinflammation.

Neuropathic pain caused by a peripheral nerve injury constitutes a great challenge in clinical treatments due to the unsatisfactory efficacy of the current strategy. Microglial activation-mediated neuroinflammation is a major characteristic of neuropathic pain. Oleanolic acid is a natural triterpenoid in food and medical plants, and fulfills pleiotropic functions in inflammatory diseases. Nevertheless, its role in neuropathic pain remains poorly elucidated. In the current study, oleanolic acid dose-dependently suppressed LPS-evoked IBA-1 expression (a microglial marker) without cytotoxicity to microglia, suggesting the inhibitory efficacy of oleanolic acid in microglial activation. Moreover, oleanolic acid incubation offset LPS-induced increases in the iNOS transcript and NO releases from microglia, concomitant with the decreases in pro-inflammatory cytokine transcripts and production including IL-6, IL-1ß, and TNF-α. Simultaneously, oleanolic acid shifted the microglial polarization from the M1 phenotype to the M2 phenotype upon LPS conditions by suppressing LPS-induced M1 marker CD16, CD86 transcripts, and enhancing the M2 marker Arg-1 mRNA and anti-inflammatory IL-10 levels. In addition, the LPS-induced activation of TLR4-NF-κB signaling was suppressed in the microglia after the oleanolic acid treatment. Restoring this signaling by the TLR4 plasmid transfection overturned the suppressive effects of oleanolic acid on microglial polarization-evoked inflammation. In vivo, oleanolic acid injection alleviated allodynia and hyperalgesia in SNL-induced neuropathic pain mice. Concomitantly, oleanolic acid facilitated microglial polarization to M2, accompanied by inhibition in inflammatory cytokine levels and activation of TLR4-NF-κB signaling. Collectively, these findings confirm that oleanolic acid may ameliorate neuropathic pain by promoting microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype via the TLR4-NF-κB pathway, thereby indicating its usefulness as therapeutic intervention in neuropathic pain.

Claudin-15 overexpression inhibits proliferation and promotes apoptosis of Schwann cells in vitro.

Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury. However, how Claudin-15 affects Schwann cell function is still unknown. This study aimed to identify the effects of Claudin-15 on proliferation and apoptosis of Schwann cells cultured in vitro and explore the underlying mechanisms. Primary Schwann cells were obtained from rats. Claudin-15 in Schwann cells was knocked down using siRNA (siRNA-1 group) compared with the negative control siRNA transfection group (negative control group). Claudin-15 in Schwann cells was overexpressed using pGV230-Claudin-15 plasmid (pGV230-Claudin-15 group). The pGV230 transfection group (pGV230 group) acted as the control of the pGV230-Claudin-15 group. Cell proliferation was analyzed with EdU assay. Cell apoptosis was analyzed with flow cytometric analysis. Cell migration was analyzed with Transwell inserts. The mRNA and protein expressions were analyzed with quantitative polymerase chain reaction assay and western blot assay. The results showed that compared with the negative control group, cell proliferation rate was up-regulated; p-AKT/AKT ratio, apoptotic rate, p-c-Jun/c-Jun ratio, mRNA expression of protein kinase C alpha, Bcl-2 and Bax were down-regulated; and mRNA expression of neurotrophins basic fibroblast growth factor and neurotrophin-3 were increased in the siRNA-1 group. No significant difference was found in cell migration between the negative control and siRNA-1 groups. Compared with the pGV230 group, the cell proliferation rate was down-regulated; apoptotic rate, p-c-Jun/c-Jun ratio and c-Fos protein expression increased; mRNA expression of protein kinase C alpha and Bax decreased; and mRNA expressions of neurotrophins basic fibroblast growth factor and neurotrophin-3 were up-regulated in the pGV230-Claudin-15 group. The above results demonstrated that overexpression of Claudin-15 inhibited Schwann cell proliferation and promoted Schwann cell apoptosis in vitro. Silencing of Claudin-15 had the reverse effect and provided neuroprotective effect. This study was approved by the Experimental Animal Ethics Committee of Jilin University of China (approval No. 2016-nsfc001) on March 5, 2016.

miR-485-5p suppresses Schwann cell proliferation and myelination by targeting cdc42 and Rac1.

Schwann cells, a crucial element in peripheral nervous system, play important roles after peripheral nerve injury. In recent years, the role of miR-485-5p has been discovered in neurological diseases. However, the involvement of miR-485-5p and peripheral nerve injury remains unknown. Mice were subjected to sciatic nerve crush to mimic peripheral nerve injury and the expression of miR-485-5p was detected in sciatic nerve stumps by real-time PCR. BrdU assay was used to analyze the proliferation of Schwann cells after transfection with miR-485-5p mimic and miR-485-5p inhibitor. The effect of miR-485-5p on Schwann cell myelination was determined by evaluating levels of cyclic adenosine monophosphate (cAMP)-induced myelin-associated proteins, including Krox20 and MBP, as well as the coculture of Schwann cells and dorsal root ganglion (DRG) neurons via immunostaining with anti-MBP antibodies. The regulation mechanism of miR-485-5p was measured by bioinformatics analysis, luciferase reporter assay, and real-time PCR and Western blot. We found miR-485-5p expression was downregulated post nerve injury. miR-485-5p mimic significantly suppressed the proliferation and cAMP-induced expression levels of Krox20 and MBP in Schwann cells. Conversely, miR-485-5p inhibitor promoted these changes in Schwann cells. Also, miR-485-5p inhibitor elevated MBP-positive myelinated fibers. Cdc42 and Rac1 are targets of miR-485-5p in Schwann cells. Downregulation of cdc42 reversed the effect of miR-485-5p inhibitor on the proliferation of Schwann cells. And reducing Rac1 expression attenuated the effect of miR-485-5p silencing on Schwann cell myelination. In conclusion, this study indicated that miR-485-5p suppressed the proliferation and myelination of Schwann cells via targeting cdc42 and Rac1. Which may provide a novel method for the treatment of peripheral nerve injury.

Improved functional outcome in NTOS patients following resection of the subclavius muscle with radiological signs of nerve impingement: indication of participation of the subclavius in brachial plexus compression.

OBJECTIVE: Both clinical and radiological reports have suggested that the subclavius, a muscle in the costoclavicular space of the thoracic outlet, participates in neurogenic thoracic outlet syndrome (NTOS) in some instances, especially during movements narrowing the costoclavicular space. Magnetic resonance imaging can identify subclavius muscles with signs of nerve impingement, yet the impact of the subclavius in such situations remains unclear. Therefore, the authors investigated whether dividing or sparing the subclavius characterized by nerve impingement on MRI would affect surgical outcomes. METHODS: In this retrospective nonrandomized study, authors analyzed all NTOS patients with a subclavius muscle characterized by nerve impingement on MRI (loss of normal fat planes surrounding the brachial plexus) in the period between March 2010 and November 2016. Patients were divided into two groups: the sparing group, in which patients had undergone conventional supraclavicular scalenectomy and first rib resection (FRR), and the dividing group, in which patients had undergone scalenectomy, FRR, and subclavius dividing using a modified supraclavicular incision. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, a shoulder range of motion subscale (DASH items 6, 12-15, and 19) concerning overhead activities that can significantly narrow the costoclavicular space, postoperative MRI studies, and patient self-assessments were used to assess surgical outcomes. Univariate and multivariate analyses were conducted to identify independent factors associated with subscale scores. RESULTS: From a total of 261 patients screened, 71 were eligible for study inclusion. Compared with the sparing group (33 patients), the dividing group (38 patients) had similar postoperative DASH scores and self-assessments but better subscale scores (9.50 ± 2.76 vs 11.94 ± 2.87, p = 0.0005). Postoperative MRI on hyperabduction showed that the brachial plexus became surrounded by normal fat tissue in the costoclavicular space in the diving group but still had signs of impingement from the untreated subclavius muscle in the sparing group. This observation agreed with a better functional recovery in terms of overhead activities in the dividing group, which was reflected by better subscale scores. Multivariate analyses indicated that the type of treatment and symptom duration prior to surgery influenced the subscale scores independently. CONCLUSIONS: This study revealed that an untreated radiological nerve-compressing subclavius muscle could lead to a relatively lower degree of recovery in the ability to perform overhead activities for NTOS patients postoperatively, suggesting that such subclavius muscles may participate in positional brachial plexus compression during movements narrowing the costoclavicular space. Dividing the muscles could decompress the costoclavicular space more effectively and may lead to better functional recovery.

MicroRNA-145-3p suppresses proliferation and promotes apotosis and autophagy of osteosarcoma cell by targeting HDAC4.

Studies have shown that miR-145-3p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the mechanism of a tumor suppressor of miR-145-3p. The expressions of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. The proliferation ability was examined by MTT assay. The apoptosis and autophagy of cells were monitored by flow cytometry and microcopy, respectively. The regulation of miR-145-3p on HDAC4 was determined by luciferase assays and western blot assay. The results showed that miR-145-3p was significantly reduced in the osteosarcoma compared with the normal bone tissue. Overexpression of miR-145-3p significantly attenuated the proliferation and induced the apoptosis and autophagy of osteosarcoma cells. Furthermore, we demonstrated that miR-145-3p has inhibited the malignant behavior of osteosarcoma by down-regulating HDAC4 expression. These findings suggested that miR-145-3p may act as a tumor suppressor in osteosarcoma. MiR-145-3p/HDAC4 may be a novel therapeutic target in treatment of osteosarcoma.

miR-182 promotes cell proliferation and invasion by inhibiting APC in melanoma.

OBJECTIVE: Common treatment methods have shown a lack of therapeutic effect in melanoma, a type of malignant tumor. The pathogenesis of melanoma is not yet fully clear, therefore, search for a new treatment strategy is urgent. Recent studies have demonstrated that miR-182 is remarkably over-expressed in human melanoma. Our study aimed to explore the underlying mechanism of miR-182 on melanoma. METHODS: In this study, the expression level of miR-182 was detected using RT-PCR in melanoma and adjacent tissues as well as in HEM-m, A375, A2058, and WM35 cell lines. Functions of miR-182 were investigated by using CCK-8 on cell proliferation, apoptosis, invasion, and cell cycle on A375 cells. Moreover, expression levels of Frz, Dsh, ß-catenin, APC, Axin, GSK-3ß, and CK1 were detected by Western blotting after knockdown and overexpression of miR-182. Overexpression of miR-182 and knockdown of APC was used to demonstrate regulated functions in melanoma. RESULTS: Expression levels of miR-182 were significantly upregulated in melanoma tissues and cell lines. Overexpression of miR-182 promoted cell proliferation, migration, and invasion while inhibiting cell apoptosis and cell cycle in S phase. Overexpression of miR-182 upregulated expression levels of ß-catenin and APC. Overexpression of miR-182 and knockdown of APC inhibited proliferation of melanoma cells and tumors. CONCLUSION: Overexpression of miR-182 promotes cell proliferation and invasion by targeting to APC in melanoma. The pathogenesis of miR-182 and APC might provide therapeutic targets for treatment of melanoma in the molecular level.

Tendon transfer to restore the extension of the thumb using the extensor carpi radialis brevis: A long-term follow-up.

PURPOSE: The present study aimed to investigate the long-term functional and clinical outcomes of a tendon transfer to restore the extension of the thumb using the extensor carpi radialis brevis. METHODS AND MATERIALS: From June 2005 to September 2012, eight patients (six males; two females) with a mean age of 30 years (range, 16-52 years) who suffered rupture or division of extensor pollicis longus underwent a tendon transfer to restore the extension of the thumb using the extensor carpi radialis brevis. The range of motion, pinch, and grip strength of thumb were compared with the nonoperated hand and evaluated for all the study patients using the Geldmacher scoring system. RESULTS: At an average follow-up of 56 months, all eight patients could extend their thumbs fully and were assessed as good or excellent according to the Geldmacher scoring system. Average grip and tip pinch strengths of the operated hand were 95% (34.9 kg ± 14.0 kg vs. 36.6 kg ± 14.6 kg) and 92% (9.2 kg ± 4.8 kg vs. 9.9 kg ± 4.7 kg) of the nonoperative side, respectively. There was no marked loss of extension motion or strength of the wrist nor any other postoperative complications. CONCLUSIONS: The procedure of transferring the extensor carpi radialis brevis tendon to the extensor pollicis longus provides excellent long-term clinical results for restoring the extension of the thumb. The procedure is safe, with few complications, and it can be an alternate procedure of restoring the extension of the thumb.

Epigenetic upregulation of Cdk5 in the dorsal horn contributes to neuropathic pain in rats.

Numerous reports have shown that cyclin-dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, critically contributes to the induction and maintenance of chronic pain induced by peripheral inflammation and nerve injury. Recent evidence has also suggested the critical role of an epigenetic mechanism in the setting of chronic pain. The present study aims to elucidate the cyclic AMP response element-binding protein (CREB)-mediated upregulation of Cdk5 and its functional significance in rats with neuropathic pain induced by chronic constriction injury (CCI) in the sciatic nerve. Significantly increased expression of Cdk5 was observed in the dorsal horn of rats with CCI, and intrathecal delivery of Cdk5 inhibitor roscovitine significantly attenuated the mechanical allodynia in these rats. Phosphorylation of CREB and its occupancy in the Cdk5 promoter region was also increased in the dorsal horn, which led to increased histone H4 acetylation in the Cdk5 promoter region and the upregulated transcription of Cdk5. Inhibition of CREB activity attenuated the upregulation of Cdk5 and alleviated the mechanical allodynia in rats with CCI. These results demonstrated a CREB-mediated epigenetic upregulation of Cdk5 in the dorsal horn, which critically contributed to the maintenance of painful behavior in the rats with neuropathic pain.