[Retracted] MicroRNA­643 regulates the expression of ZEB1 and inhibits tumorigenesis in osteosarcoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell invasion and migration assay data shown in Fig. 2E and 4E, and the immunohistochemical data shown in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 5157­5164, 2017; DOI: 10.3892/mmr.2017.7273].

Integrated Bioinformatics-Based Identification of Potential Diagnostic Biomarkers Associated with Diabetic Foot Ulcer Development.

The present study was designed to detect possible biomarkers associated with diabetic foot ulcer (DFU) incidence in an effort to develop novel treatments for this condition. The GSE7014 and GSE29221 gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, after which differentially expressed genes (DEGs) were identified between DFU and healthy samples. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were performed to explore the functional roles of these genes. In total, 1192 DEGs were identified in the GSE7014 dataset (900 upregulated, 292 downregulated), while 1177 were identified in the GSE29221 dataset (257 upregulated, 919 downregulated). GO analyses revealed these DEGs to be significantly enriched in biological processes including sarcomere organization, muscle filament sliding, and the regulation of cardiac conduction, molecular functions including structural constituent of muscle, protein binding, and calcium ion binding, and cellular components including Z disc, myosin filament, and M band. These DEGs were also enriched in the adrenergic signaling in cardiomyoctes, dilated cardiomyopathy, and tight junction KEGG pathways. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with DFU development.

Functional Analysis of Estrogen Receptor 1 in Diabetic Wound Healing: A Knockdown Cell-Based and Bioinformatic Study.

BACKGROUND Diabetic wound (DW) treatment is a serious challenge for clinicians, and the underlying mechanisms of DWs remain elusive. We sought to identify the critical genes in the development of DWs and provide potential targets for DW therapies. MATERIAL AND METHODS Datasets of GSE38396 from the Gene Expression Omnibus (GEO) database were reviewed. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology term analyses were carried out, and Cytoscape software (Cytoscape 3.7.2) was used to construct the protein interaction network. Serum samples from patients with diabetes and control participants were collected, and the expression of estrogen receptor 1 (ESR1) was measured by quantitative reverse-transcription polymerase chain reaction. In addition, the function of ESR1 in human skin fibroblasts was investigated in vitro. RESULTS Eight samples were analyzed using the Morpheus online tool, which identified 637 upregulated and 448 downregulated differentially expressed genes. The top 5 KEGG pathways of upregulated differentially expressed genes were associated with sphingolipid metabolism, estrogen signaling, ECM-receptor interaction, MAPK signaling, and PI3K-Akt signaling. The hub genes for DWs were JUN, ESR1, CD44, SMARCA4, MMP2, BMP4, GSK3B, WDR5, PTK2, and PTGS2. JUN, MMP2, and ESR1 were the upregulated hub genes, and ESR1 was found to be consistently enriched in DW patients. Inhibition of ESR1 had a stimulative role in human skin fibroblasts. CONCLUSIONS ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing.

Research on the repairing effect of polylactic acid-trimethylene carbonate/GNDF slow-release catheter on the injured femoral nerve fiber.

Present research aims to investigate the repairing effect of polylactic acid-trimethylene carbonate/GNDF slow-release catheter on the injured femoral nerve fiber. Adult SD male rats as the subjects were divided into two groups, the GDNF group and the control group, and received the surgery to remove the nerve from the exposed left femoral nerves. Thereafter, rats in the GNDF group and the control group received the GNDF or normal saline, and we evaluated the changes in rats, including the morphological, functional and electrophysiological changes of regenerated nerves. Regenerated axons were found in each group, but enormous regeneration of axons was only identified in GDNF group. Further analysis showed that: At the 4th, 8th and 12th weeks, areas of the regenerated nerves in GDNF group were (0.95±0.06) mm2, (1.14±0.07) mm2 and (1.22±0.06) mm2, respectively; in the control group, these were (0.15±0.01) mm2, (0.25±0.07) mm2 and (0.52±0.05) mm2, respectively. These showed that the outcome of GDNF group was superior to that of control group. In GDNF group, quantities of the myelinated fiber were (0.8119×104±0.0637×104), (1.3371×104±0.0460×104) and (1.7669×104±0.0542×104); while in control group, these were (0.2179×104±0.0097×104), (0.3490×104±0.0329×104) and (0.7737×l04±0.0788×104). Again, these results also indicated that the outcome of GDNF group was superior to that of the control group (p<0.05). In GDNF group, the average diameters of myelinated fibers were (2.25±0.17) µm, (2.42±0.14) µm and (2.80±0.10) µm, which were significantly better than (1.24±0.08) µm, (1.43±0.14) µm and (1.82±0.14) µm in the control group. Degrees of fiber myelination in the GDNF group were (0.71±0.03), (0.64±0.03) and (0.6l±0.0l), respectively, which were also significantly higher than (0.02±0.01), (0.04±0.01) and (0.06±0.02) in the control group (p<0.01). At the 12th week after surgery, HE staining was performed to observe the histological changes in quadriceps femoris for evaluation of atrophy in each group. In the GDNF group, significant amelioration was found in the atrophy of quadriceps femoris with an average area of myofiber of (84.95±3.92) %, while the area of the control group was (57.95±5.78) %, suggesting that the outcome of the GDNF group was better than that of the control group (p<0.05). Electrophysiological examination of nerves was employed to detect the recovery of neurological functions after repair of nerve defect. At the 4th, 8th and 12th weeks after surgery, CMAP amplitudes in the GDNF group were (9.34±0.52) mV, (14.40±0.69) mV and (19.18±0.48) mV, significantly better than (0.39±0.07) mV, (1.44±0.41) mV and (9.27±0.40) in the control group (p<0.01). Polylactic acid-trimethylene carbonate/GNDF slow-release catheter can accelerate the functional recovery of injured nerves, thus promoting the regeneration efficiency of femoral nerves.

MicroRNA­643 regulates the expression of ZEB1 and inhibits tumorigenesis in osteosarcoma.

Osteosarcoma is among the most malignant types of tumor worldwide and has become a leading contributor to tumor incidence, particularly in adolescents. Resistance to conventional treatment and the complexity of osteosarcoma tumorigenesis has resulted in high mortality rates. MicroRNAs are a class of noncoding RNAs, which regulate numerous biological processes. However, the involvement of miR­643 in osteosarcoma remains to be elucidated. In the present study, reverse transcription­quantitative polymerase chain reaction, luciferase reporter assay, invasion assay, viability assay, western blot analysis and in vivo implantation were performed to analyze the action of miR­643 in osteosarcoma. The results demonstrated that miR­643 inhibited the progression of osteosarcoma and acted as a potential tumor suppressor. The expression of miR­643 was downregulated in osteosarcoma tissues and cell lines. In addition, miR­643 transfection significantly impaired the proliferation and invasion of osteosarcoma cells. The present study also identified Zinc finger E­box­binding homeobox 1 (ZEB1) as a direct target of miR­643, and the ectopic expression of ZEB1 counteracted the effect of miR­643 transfection. A significant inverse correlation was also found between the expression of miR­643 and ZEB1. A low expression of miR­643 or a high expression of ZEB1 was associated with poor patient survival rates. The results of the present study suggested that the decreased expression of miR­643 may be involved in the mechanism underlying the development of osteosarcoma. The intricate interactions between miR­643 and ZEB1 may serve as a potential therapeutic target in osteosarcoma oncogenesis.

Height and Risk of Hip Fracture: A Meta-Analysis of Prospective Cohort Studies.

The association between height and risk of hip fracture has been investigated in several studies, but the evidence is inconclusive. We therefore conducted this meta-analysis of prospective cohort studies to explore whether an association exists between height and risk of hip fracture. We searched PubMed and EMBASE, Web of Science, and the Cochrane Library for studies of height and risk of hip fracture up to February 16, 2016. The random-effects model was used to combine results from individual studies. Seven prospective cohort studies, with 7,478 incident hip fracture cases and 907,913 participants, were included for analysis. The pooled relative risk (RR) was 1.65 (95% confidence interval (CI): 1.26-2.16) comparing the highest with the lowest category of height. Result from dose-response analysis suggested a linear association between height and hip fracture risk (P-nonlinearity = 0.0378). The present evidence suggests that height is positively associated with increased risk of hip fracture. Further well-designed cohort studies are needed to confirm the present findings in other ethnicities.

Correlation of Adrenomedullin Concentrations with Knee Osteoarthritis Grade.

BACKGROUND Adrenomedullin, a recently identified myokine, has an anti-inflammatory effect. Therefore, we aimed to assess the correlation of adrenomedullin concentrations with the presence and grade of severity of knee osteoarthritis (OA). MATERIAL AND METHODS We recruited 187 knee OA patients and 109 healthy subjects. The severity of OA was evaluated using the Kellgren-Lawrence grading system. RESULTS Compared with the control group, the knee OA group revealed markedly higher adrenomedullin concentrations. Serum and synovial fluid (SF) adrenomedullin concentrations increased with increased KL grades. CONCLUSIONS Serum and SF adrenomedullin concentrations show a correlation with the severity of knee OA.

Operative versus non-operative treatment in complex proximal humeral fractures: a meta-analysis of randomized controlled trials.

Whether operative treatment for complex proximal humeral fractures (CPHFs) has a greater benefit over non-operative treatment remains controversial. There is no consensus on the optimal treatment in elderly patients with CPHFs. This updated meta-analysis of randomized controlled trials (RCTs) aims to investigate whether operative treatment is superior to non-operative treatment in CPHFs. The authors searched RCTs in the electronic databases (Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Medline, Embase, Springer Link, Web of Knowledge, OVID and Google Scholar) from their establishment to July 2015. Researches on operative and non-operative treatment for CPHFs were selected in this meta-analysis. The quality of all studies was assessed and effective data was pooled for this meta-analysis. Outcome measurements were functional status include constant scores (CS scores) and disabilities of the arm, shoulder and hand scores (DASH scores), total complication rates and healthy-related quality of life. The meta-analysis was performed with software revman 5.3. Nine articles with a total 518 patients (average age 70.93) met inclusion criteria. Patients were followed up for at least 1 year in all the studies. No statistical differences were found between operative and non-operative treatment in CS scores at 12 mo (months) [MD 1.06 95 % CI (-3.51, 5.62)] and 24 mo [MD -0.61 95 % CI (-5.87, 4.65)]. There are also no statistical differences between operative and non-operative treatment in DASH scores at 12 mo [MD -4.51 95 % CI (-13.49, 4.47)] and 24 mo [MD -7.43 95 % CI (-16.14, 1.27)]. Statistical differences were found between operative and non-operative treatment in total complication rates [RR 1.55, 95 % CI (1.24, 1.94)]. Statistical differences in EQ-5D at 24 mo [MD 0.15, 95 % CI (0.05, 0.24)] were found between operative and non-operative treatment but no statistical differences were found in ED-5D at 12 mo [MD 0.08, 95 % CI (-0.01, 0.17)], 15D at 12 mo [MD 0.02, 95 % CI (-0.68, 0.73)] and 15D at 24 mo [MD 0.02, 95 % CI (-0.07, 0.83)]. Operative treatments did not significantly improve the functional outcome and healthy-related quality of life in elderly patients. Instead, Operative treatment for CPHFs led to higher incidence of postoperative complications.

Effects of valproic Acid on axonal regeneration and recovery of motor function after peripheral nerve injury in the rat.

BACKGROUND: Valproic acid (VPA) is used to be an effective anti-epileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal regulated kinase pathway, and increases bcl-2 and growth cone-associated protein 43 levels in spinal cord. In the present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. METHODS: The rats in VPA group and control group were administered with valproic acid (300mg/kg) and sodium chloride respectively after operation. Each animal was observed sciatic nerve index (SFI) at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. RESULTS: There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the VPA group and controls (P<0.05). CONCLUSIONS: The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.

Enhanced rat sciatic nerve regeneration through silicon tubes implanted with valproic acid.

Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal-regulated kinase pathway, and increase B-cell lymphoma/leukemia-2 (bcl-2)and growth cone-associated protein 43 (GAP-43) levels in spinal cord. We hypothesized that VPA could enhance axonal regeneration in the rat. In the present research, we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function through a silicon tube implanted with VPA. The left sciatic nerves were exposed through dorsal-splitting incisions, and 8-mm nerve sections were excised at the middle of the thigh. Then, a 1.0-cm-long silicone tube (internal diameter,1.0 mm; exterior diameter, 2.0 mm) was used to bridge the nerve deficit, anchored to the proximal and distal terminals of the excised deficit of sciatic nerves with 9-0 nylon epineural suture. Sterile petroleum jelly was used to seal the ends of the tubes to avoid leakage. The rats in the VPA group and control group were locally delivered 10 muL VPA injection (400 mg/5 mL) and normal saline, respectively, after the operation. The sciatic nerve index (SFI) was observed in each animal at 2-week intervals and electrophysiology was studied at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment (12 weeks after the operation). Using the digital image-analysis system, the thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, amplitude of activity potential), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the VPA group and controls ( P < 0.05). The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.

[Treatment of fracture of neck of femur in the aged with hollow compression screw].

OBJECTIVE: To summarize the clinical results of hollow compression screw in treatment of fracture of neck of femur in the aged. METHODS: From November 1993 to October, 1998, 52 aged patients with several types of fracture of neck of femur were treated; among them, there were 25 males and 27 females aged from 60 to 83 years (70 years on average). There were 48 cases of fresh fracture and 4 cases of old fracture. Forty-two cases were performed closed reduction internal fixation, 10 cases with open reduction internal fixation. RESULTS: All the patients could sit by themselves 4 to 6 days after operation, and could walk with a crutch 10 to 15 days after operation. The mobility of hip joint was nearly normal 4 weeks after operation. All the patients were followed 26 to 84 months, 48.5 months on average. Bone union was achieved in 50 cases, nonunion in 2 cases. The average healing time was 4.7 months. There were no other complications, such as ankylosis and muscular atrophy, but ischemic necrosis in 3 cases. CONCLUSION: This method has following advantages, convenient manipulation, less injury, stable fixation, and the short-term recovery, which avoid some common complications. It is a reliable method worthy of popularizing.