[Retracted] Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell invasion and migration assay data shown in Fig. 6 and the cell proliferation assay experiments shown in Fig. 2 were strikingly similar to data appearing in different form in other articles by different authors; furthermore, in Fig. 2, for the '10 mM metformin' experiment, certain of the glioma cells appeared to be strikingly similar to other cells contained within the same data panels. 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, and owing to concerns with the authenticity of certain of the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 887­894, 2019; DOI: 10.3892/mmr.2019.10369].

Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis.

Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies.

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

Advances in experimental models of osteonecrosis of the femoral head.

Background: Osteonecrosis of the femoral head (ONFH) is a devastating disease affecting young adults, resulting in significant pain, articular surface collapse, and disabling dysfunction. ONFH can be divided into two broad categories: traumatic and non-traumatic. It has been established that ONFH results from an inadequate blood supply that causes the death of osteocytes and bone marrow cells. Nonetheless, the precise mechanism of ONFH remains to be elucidated. In this regard, preclinical animal and cell models to study ONFH have been established to assess the efficacy of various modalities for preventing and treating ONFH. Nevertheless, it should be borne in mind that many models do not share the same physiologic and metabolic characteristics as humans. Therefore, it is necessary to establish a reproducible model that better mimics human disease. Methods: We systematically reviewed the literatures in regard to ONFH experimental models over the past 30 years. The search was performed in PubMed and Web of Science. Original animal, cell studies with available full-text were included. This review summarizes different methods for developing animal and cell experimental models of ONFH. The advantages, disadvantages and success rates of ONFH models are also discussed. Finally, we provide experimental ONFH model schemes as a reference. Results: According to the recent literatures, animal models of ONFH include traumatic, non-traumatic and traumatic combined with non-traumatic models. Most researchers prefer to use small animals to establish non-traumatic ONFH models. Indeed, small animal-based non-traumatic ONFH modeling can more easily meet ethical requirements with large samples. Otherwise, gradient concentration or a particular concentration of steroids to induce MSCs or EPCs, through which researchers can develop cell models to study ONFH. Conclusions: Glucocorticoids in combination with LPS to induce ONFH animal models, which can guarantee a success rate of more than 60% in large samples. Traumatic vascular deprivation combines with non-traumatic steroids to induce ONFH, obtaining success rates ranging from 80% to 100%. However, animals that undergo vascular deprivation surgery may not survive the glucocorticoid induction process. As for cell models, 10-6mol/L Dexamethasone (Dex) to treat bone marrow stem cells, which is optimal for establishing cell models to study ONFH. The translational potential of this article: This review aims to summarize recent development in experimental models of ONFH and recommended the modeling schemes to verify new models, mechanisms, drugs, surgeries, and biomaterials of ONFH to contribute to the prevention and treatment of ONFH.

A comparison of radiological and clinical outcomes between robotic-assisted and conventional total hip arthroplasty: A meta-analysis.

BACKGROUND: The purpose of this study was to investigate whether robotic-assisted total hip arthroplasty (RATHA) is superior to conventional total hip arthroplasty (CTHA) in terms of radiological and clinical outcomes. METHODS: Three databases (PubMed, Cochrane Library, and Embase) were searched for articles published before 11 May 2021. The comparison outcomes of interest included radiological and clinical outcomes. RESULTS: Eighteen studies involving 2845 hips that compared the radiological and clinical outcomes of RATHA and CTHA were included in this study. There was no significant difference between RATHA and CTHA in cup anteversion or complications. However, RATHA showed better outcomes in terms of leg-length discrepancy, stem alignment, cup inclination, the Lewinnek safe zone, Callanan safe zone, total complications, and intraoperative complications. Robotic-assisted total hip arthroplasty was inferior to CTHA in terms of operative time and dislocations (all p-values < 0.05). CONCLUSIONS: The radiological and clinical outcomes of RATHA were comparable and even better than those of CTHA, except for operative time and dislocation outcomes.

Pelvic incidence-guided reduction in transverse parts of U-shaped sacral fractures: Technical recommendations.

OBJECTIVE: The purpose of this study is to present a surgical technique that simultaneously reduces and fixates the transverse parts of U-shaped sacral fractures. METHODS: The sacral fracture was exposed through a posterior median approach. In a flexion injury, the rotation of the lower sacral segment is reduced by distraction along a pre-curved rod. Then, lordotic restoration is performed with a Weber clamp placed at the lower sacral segment through dragging. In an extension injury, longitudinal distraction is performed along the spinopelvic rod to reduce the vertical displacement. Next, the transverse displacement is reduced by a dissector placed between the upper and lower sacral segments through levering. The sagittal reduction on the lateral pelvic view was judged by PI. A regression analysis of Oswestry disability index (ODI) with Z-scores of PI, lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT) was performed. RESULTS: At the 1-year follow-up, the average PI, LL, SS, and PT values were 51.6 (range: 43.1-76.0), 44.8 (34.6 - 60.1), 35.4 (18.1 - 48.0), and 16.7 (2.2-35.4) degrees, respectively. All patients were able to maintain an upright stance. The average ODI was 27.6% (2-72%). Surprisingly, the regression analysis demonstrated a significant linear relationship between ODI and LL (R2 = 0.367, p = .048) but not between ODI and PI (R2 = 0.227, p = .138). CONCLUSIONS: Using PI as guidance, the surgical procedures were helpful to reduce the PI of transverse sacral fractures into the normal range. However, the relationship between PI and the prognosis remains to be evaluated by future researches.

Sacral osteotomy combined with triangular osteosynthesis in the treatment of malunion and nonunion of vertically displaced pelvic fractures.

BACKGROUND: Malunion and nonunion of vertically displaced pelvic fractures result in lower limb length discrepancies, claudication, and pain. There have been few previous reports of this type of corrective surgery for these old pelvic fractures. We present a surgical technique of sacral osteotomy combined with triangular osteosynthesis in the treatment of malunion and nonunion of vertically displaced pelvic fractures and report on its short-term clinical results. METHODS: We retrospectively reviewed nine patients (five males and four females) with malunion or nonunion of vertically displaced pelvic fractures treated with sacral osteotomy and triangular osteosynthesis from April 2015 to January 2020. The age ranged from 14 to 45 years (average, 30.7 years). The time from injury to deformity correction surgery ranged from 3 months to 5 years (average, 12.8 months). The vertical displacement of a unilateral hemipelvis was 3.0-4.5 cm (average, 3.80 cm). According to AO/OTA classification at the initial fracture, there are eight cases in type C1.3 and one case in type C3.3. Sacral osteotomy and triangular osteosynthesis were used in all nine patients. The degree of unilateral hemipelvic reduction was assessed postoperatively based on measurements from the anteroposterior (AP) X-ray. Majeed score and pain visual analog scale (VAS) were used to assess the therapeutic effect of the patients during follow-up. RESULTS: In all nine patients, postoperative AP X-ray showed correction displacement of 1.7-3.9 cm (average, 3.20 cm). All the patients were followed up for 6-36 months (average, 12.7 months). At the last follow-up, the Majeed score of pelvic fracture increased from an average of 53.9 points (30-84 points) preoperatively to 87.0 points (72-94 points), and the VAS score for pain decreased from an average of 6.0 points (4-8 points) preoperatively to 1.2 points (0-3 points). None had complications like infection, implant broken, screw loosening, iatrogenic nerve, and blood vessel injury. CONCLUSION: Sacral osteotomy combined with triangular osteosynthesis for the treatment of pelvic malunion and nonunion caused by sacral fractures can correct significantly vertical displacement of a unilateral pelvis, prolong limb length, and reconstruct the stability of a pelvic ring, achieving good clinical results.

Outpatient total knee and hip arthroplasty present comparable and even better clinical outcomes than inpatient operation.

Background: The purpose of this study was to compare total complications, complications stratified by type, readmissions, and reoperations at 30 and 90 days after outpatient and standard inpatient total knee and total hip arthroplasty (TKA, THA). Methods: A literature search was conducted from the PubMed, Cochrane Library, and Embase databases for articles published before 20 August 2021. The types of studies included prospective randomized controlled trials, prospective cohort studies, retrospective comparative studies, retrospective reviews of THA and TKA registration databases, and observational case-control studies. Comparisons of interest included total complications, complications stratified by type, readmissions, and reoperations at 30 and 90 days. The statistical analysis was performed using Review Manager 5.3. Results: Twenty studies with 582,790 cases compared relevant postoperative indicators of outpatient and inpatient total joint arthroplasty (TJA) (TKA and THA). There was a significant difference in the total complications at 30 days between outpatient and inpatient THA (p = 0.001), readmissions following TJA (p = 0.03), readmissions following THA (p = 0.001), stroke/cerebrovascular incidents following TJA (p = 0.01), cardiac arrest following TJA (p = 0.007), and blood transfusions following TJA (p = 0.003). The outcomes showed an obvious difference in 90-day total complications between outpatient and inpatient TJA (p = 0.01), readmissions following THA (p = 0.002), and surgical-related pain following TJA (p < 0.001). We did not find significant differences in the remaining parameters. Conclusion: Outpatient procedures showed comparable and even better outcomes in total complications, complications stratified by type, readmissions, and reoperations at 30 and 90 days compared with inpatient TJA for selected patients.

Corrigendum: A Coronal Landmark for Tibial Component Positioning With Anatomical Alignment in Total Knee Arthroplasty: A Radiological and Clinical Study.

[This corrects the article DOI: 10.3389/fsurg.2022.847987.].

Total hip arthroplasty for treatment of femoral neck fracture due to hypophosphatemic osteomalacia: a retrospective case series with mean follow-up of five years.

BACKGROUND: To retrospectively characterize the clinical characteristics and efficacy of total hip arthroplasty and the important factors needing attention in hypophosphatemic osteomalacia (HO) patients with hip involvement. PATIENTS AND METHODS: We performed a review of seven patients (two women and five men) referred to our clinic with a final diagnosis of HO who received total hip arthroplasty between 2010 and 2018. Five patients (Group 1) received proper medical management with or without aetiologic therapy, while the other two patients (Group 2) did not receive due to misdiagnosis. The mean follow-up duration was 5.1 ± 2.0 years. RESULTS: The patients in Group 1 had significant relief of pain and improved laboratory results. The mean Harris Hip Score of Group 1 increased from 44.2 ± 6.0 to 94.0 ± 3.0, and the mean VAS score decreased from 8.8 ± 0.4 to 1.8 ± 0.7. However, the progressive extensive pain score in Group 2 had no obvious improvement, with the Harris Hip Score increasing from 45.5 ± 0.5 to 60 ± 28.0 and the VAS score decreasing from 9.0 ± 1.0 to 6.5 ± 2.5. CONCLUSION: THA appears to be an effective method for hip arthritis or joint deformities resulting from hypophosphatemic osteomalacia. A satisfactory outcome of the surgery depends on the early etiological identification, the treatment of hypophosphatemia, a careful operation, and the operative strategies, as well as proper medical treatment.

Knockdown of HDAC9 Inhibits Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Partially by Suppressing the MAPK Signaling Pathway.

Background: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation. Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs. Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator. Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH.

A Coronal Landmark for Tibial Component Positioning With Anatomical Alignment in Total Knee Arthroplasty: A Radiological and Clinical Study.

Objective: The purpose of this study was to investigate the value of the lateral point of articular surface of distal tibia (LADT) for anatomical alignment in total knee arthroplasty. Methods: We reconstructed 148 three-dimensional pre-arthritic tibias and measured the tibial component inclination angle corresponding to the distal landmark of LADT. A retrospective study included 81 TKA recipients divided into the AA group and MA group. Clinical assessments including ROM, HSS, WOMAC, satisfaction for surgery, and radiological assessment were evaluated at one-year follow-up. Results: The tibial component varus angle corresponding to the distal landmark of LADT in the male and female groups were 3.4 ± 0.3° (2.6~4.2°) and 3.2 ± 0.3° (2.3~4.0°), respectively (P <0.05). Using LADT as the distal landmark for extramedullary tibial cutting guidance, the medial proximal tibia angle (MPTA) of the AA group was 87.0±1.2° (85.0~90.0°), and the AA and MA technique showed no difference in improvement in postoperative knee functional recovery at final follow-up. Conclusions: This study preliminarily indicated that LADT can be a reliable and economical landmark for coronal plane alignment of the tibial component.

Knockdown of POSTN Inhibits Osteogenic Differentiation of Mesenchymal Stem Cells From Patients With Steroid-Induced Osteonecrosis.

Steroid-induced osteonecrosis of femoral head (SONFH) is a common and serious complication caused by long-term and/or excessive use of glucocorticoids (GCs). The decreased activity and abnormal differentiation of bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the major reasons for the onset and progression of this disease. Periostin (POSTN) is a matricellular protein which plays an important role in regulating osteoblast function and bone formation. Sclerostin (SOST) is a secreted antagonist of Wnt signaling that is mainly expressed in osteocytes to inhibit bone formation. However, the exact role of POSTN and SOST in SONFH has not been reported yet. Therefore, we detected the differential expression of POSTN and SOST in BMSCs of SONFH Group patients, and Control Group was patients with traumatic ONFH (TONFH) and developmental dysplasia of the hip (DDH). Furthermore, we used lentiviral transfection to knockdown POSTN expression in BMSCs of patients with SONFH to study the effect of POSTN knockdown on the SOST expression and osteogenic differentiation of BMSCs. The results indicated that the endogenous expression of POSTN and SOST in BMSCs of SONFH Group was upregulated, compared with Control Group. POSTN was upregulated gradually while SOST was downregulated gradually at days 0, 3, and 7 of osteogenic differentiation of BMSCs in Control Group. Contrarily, POSTN was gradually downregulated while SOST was gradually upregulated during osteogenic differentiation of BMSCs in SONFH Group. This could be due to increased expression of SOST in BMSCs, which was caused by excessive GCs. In turn, the increased expression of POSTN in BMSCs may play a role in antagonizing the continuous rising of SOST during the osteogenic differentiation of BMSCs in patients with SONFH. POSTN knockdown significantly attenuated osteo-specific gene expression, alkaline phosphatase activity, and calcium nodule formation in vitro; thus inhibiting the osteogenic differentiation of BMSCs in patients with SONFH. Besides, POSTN knockdown upregulated SOST expression, increased GSK-3ß activity, and downregulated ß-catenin. These findings suggest that POSTN have an essential role in regulating the expression of SOST and osteogenic differentiation of BMSCs in patients with SONFH, and POSTN knockdown suppresses osteogenic differentiation by upregulating SOST and partially inactivating Wnt/ß-catenin signaling pathway. Therefore, targeting POSTN and SOST may serve as a promising therapeutic target for the prevention and treatment of SONFH.

The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor.

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into several tissues, such as bone, cartilage, and fat. Glucocorticoids affect a variety of biological processes such as proliferation, differentiation, and apoptosis of various cell types, including osteoblasts, adipocytes, or chondrocytes. Glucocorticoids exert their function by binding to the glucocorticoid receptor (GR). Physiological concentrations of glucocorticoids stimulate osteoblast proliferation and promote osteogenic differentiation of MSCs. However, pharmacological concentrations of glucocorticoids can not only induce apoptosis of osteoblasts and osteocytes but can also reduce proliferation and inhibit the differentiation of osteoprogenitor cells. Several signaling pathways, including the Wnt, TGFß/BMP superfamily and Notch signaling pathways, transcription factors, post-transcriptional regulators, and other regulators, regulate osteoblastogenesis and adipogenesis of MSCs mediated by GR. These signaling pathways target key transcription factors, such as Runx2 and TAZ for osteogenesis and PPARγ and C/EBPs for adipogenesis. Glucocorticoid-induced osteonecrosis and osteoporosis are caused by various factors including dysfunction of bone marrow MSCs. Transplantation of MSCs is valuable in regenerative medicine for the treatment of osteonecrosis of the femoral head, osteoporosis, osteogenesis imperfecta, and other skeletal disorders. However, the mechanism of inducing MSCs to differentiate toward the osteogenic lineage is the key to an efficient treatment. Thus, a better understanding of the molecular mechanisms behind the imbalance between GR-mediated osteoblastogenesis and adipogenesis of MSCs would not only help us to identify the pathogenic causes of glucocorticoid-induced osteonecrosis and osteoporosis but also promote future clinical applications for stem cell-based tissue engineering and regenerative medicine. Here, we primarily review the signaling mechanisms involved in adipogenesis and osteogenesis mediated by GR and discuss the factors that control the adipo-osteogenic balance.

Prognostic and Clinicopathological Significance of Long Non-coding RNA PANDAR Expression in Cancer Patients: A Meta-Analysis.

Background: Long non-coding RNA PANDAR is an emerging non-coding RNA mapping to 6p21.2. It underlies metastatic progression and chromosomal instability in a variety of cancers. Despite the fact that recent studies have revealed that lncRNA PANDAR may be a potential prognostic biomarker for patients with cancer, there has still been controversy on the prognostic value of PANDAR. Methods: Databases of PubMed, Embase, SinoMed, and Web of Science were carefully searched and the literature which investigated the prognostic value of PANDAR expression among human cancers was collected for further analysis. Odds ratios (ORs) or hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled to estimate the relation between PANDAR expression and survival or clinicopathological characteristics of cancer patients. Results: There were 13 eligible studies in total, with 1,465 patients enlisted in this meta-analysis. All the eligible studies complied with the case-control study. The outcome showed that the elevated expression level of PANDAR was significantly related to poor overall survival (OS) (pooled HR 1.72, 95%CI 1.14-2.60). However, high or low expression of PANDAR did not differ in the prediction of event-free survival (EFS). Moreover, we discovered that high PANDAR expression was closely related to decreased OS in colorectal cancer (pooled HR 3.43, 95%CI 2.06-5.72) and reduced expression level of PANDAR was markedly related to poor OS (pooled HR 0.65, 95%CI 0.45-0.88) in non-small cell lung cancer. However, the expression level of PANDAR had no significant association with OS in renal cell carcinoma (pooled HR 1.19, 95%CI 0.56-2.50). Moreover, after analysis, we discovered that the high expression level of PANDAR was associated closely with the depth of invasion (pooled OR 3.95, 95%CI 2.36-6.63), lymph node metastasis (pooled OR 1.92, 95%CI 0.93-3.98), tumor stage (pooled OR 2.05, 95%CI 0.99-4.27), and distant metastasis (pooled OR 2.87, 95%CI 1.60-5.16). Conclusions: Our study revealed that increased PANDAR expression may serve as an adverse prognostic biomarker for cancer patients, thus helping the clinical decision-making process.

Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms.

The purpose of the present study was to determine the effects of metformin on the inhibition of proliferation, apoptosis, invasion and migration of A172 human glioma cells in vitro and determine the underlying mechanism. The effects of metformin at different concentrations (0, 0.1, 1 and 10 mmol/l) on the inhibition of A172 cell proliferation were detected using a 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay. Cell apoptosis was detected by flow cytometry. Caspase­3 activity was analyzed by spectrophotometry. The invasion and migration of cells were detected by Transwell assays. The levels of Bcl­2­associated X protein (Bax), B­cell lymphoma 2 (Bcl­2), AMP­activated protein kinase (AMPK), phosphorylated­(p)AMPK and mechanistic target of rapamycin (mTOR) protein expression were detected by western blot analysis, and changes in the malondialdehyde (MDA) content and activity of superoxide dismutase (SOD) were determined. Compared with the control group, metformin significantly increased the inhibition of proliferation and apoptosis, and significantly reduced the invasion and migration of A172 cells in dose­ and time­dependent manners (P<0.05). In addition, compared with the control group, metformin significantly enhanced the activity of caspase­3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl­2 proteins (P<0.05). Metformin increased the MDA content and reduced the activity of SOD in a dose­dependent manner (P<0.05). Metformin may inhibit glioma cell proliferation, migration and invasion, and promote its apoptosis; the effects may be associated with the AMPK/mTOR signaling pathway and oxidative stress.

Prognostic significance of cyclin D3 expression in malignancy patients: a meta-analysis.

BACKGROUND: As a pivotal regulator, cyclin D3 gives play to a crucial value in conversion from the G1 stage to the S stage of cell cycle, which is implicated in tumor progression, especially proliferation and migration. Recent literatures have reported that cyclin D3 could predict survival time of malignancy patients. But, its prognostic role of cyclin D3 in neoplasms remains controversial. METHODS: Databases involving EMBASE, PubMed and Web of Science were carefully searched, and literatures investigating the prognostic effect of aberrantly expressing cyclin D3 among human cancers were collected for further analysis. We used both hazards ratios and its corresponding 95% confidence intervals to evaluate the connection among the survival rate of malignancy patients and the expression of cyclin D3. RESULTS: There were 13 eligible researches involving 16 cohorts and 2395 participants which were included in this study. The outcomes suggested that highly expressing cyclin D3 was significantly correlated with worse clinical prognosis of overall survival (HR 1.88; 95% CI 1.31-2.69) and disease specific survival (HR 2.68; 95% CI 1.35-5.31). But there existed no significant connection between the elevated expression of cyclin D3 with disease free survival (HR 2.65; 95% CI 0.83-8.46), recurrence-free survival (HR 2.86; 95% CI 0.82-9.96) and progression-free survival (HR 5.24; 95% CI 0.46-60.25) of diffident kinds of malignancy patients. Moreover, we discovered that elevated cyclin D3 expression was significantly connected with decreased overall survival in lymphoma (HR 3.72; 95% CI 2.18-6.36) while no significant relevance between highly expressing cyclin D3 and the overall survival in breast cancer was obtained (HR 2.12; 95% CI 0.76-5.91). CONCLUSIONS: This meta-analysis demonstrated that highly expressing cyclin D3 might be an unfavorable prognostic biomarker for various malignancy patients, which can make great contributions to the clinical diagnosis and treatment.

The causes and management of nonunion of femoral subtrochanteric shortening osteotomy in a THA patient: a case report.

BACKGROUND: Total hip arthroplasty (THA) is considerably difficult to perform in patients with Crowe type IV developmental dysplasia of the hip (DDH). Some Crowe type IV DDH patients require a femoral subtrochanteric shortening osteotomy to equalize the length of the lower extremities and decrease the difficulty of intraoperative reduction. Subtrochanteric transverse osteotomy has been proven to have superior clinical efficacy, but some cases of nonunion occur. CASE PRESENTATION: We present the case of a 62-year-old male patient who underwent right THA with femoral subtrochanteric transverse osteotomy due to Crowe type IV DDH. Nonunion of the osteotomy occurred during the follow-up period. In July 2017, the patient underwent right THA and femoral subtrochanteric transverse osteotomy due to Crowe type IV DDH. In November 2017, a slight feeling of bone rubbing and slight pain in the hip were reported. The ends of the osteotomy had rotated and united poorly. However, the patient requested to undergo continued observation. In December 2017, the patient reported an obvious sensation of bone rubbing and aggravated hip pain. The ends of the osteotomy had rotated and continued to exhibit nonunion. On December 26, 2017, the patient was treated with plate and screw internal fixation with bone morphogenetic protein (BMP) following our suggestion. In August 2018, the ends of the osteotomy had united after internal fixation was applied. CONCLUSIONS: THA with femoral subtrochanteric transverse osteotomy exhibits good efficacy for the treatment of patients with Crowe type IV DDH. However, postoperative nonunion occurs in a small number of cases. The causes of nonunion should be analysed, and effective measures should be taken to prevent this situation. Plate and screw internal fixation with BMP is an effective treatment for nonunion of the ends of an osteotomy.

Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation.

BACKGROUND: Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. METHODS: The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and PHB were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of PHB and QCR2 was assessed by immunoblotting and immunofluorescence. FINDING: The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with PHB in the mitochondria. Overexpression of QCR2 inhibits PHB binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased PHB protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. INTERPRETATION: These results identify a novel role for QCR2, together with PHB, in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. FUND: "973" Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province.