Intramedullary nail fixation assisted by locking plate for complex subtrochanteric femur fractures: A retrospective study.

BACKGROUND: This study aims to compare therapeutic effects of two methods in complicated subtrochanteric femur fractures surgery: intramedullary nail fixation assisted with lateral monocortical locking plate versus intramedullary nail fixation assisted with supplementary cables. METHODS: From June 2015 to June 2020, seventy-seven patients with complex subtrochanteric fractures (i.e., Seinsheimer's classification type IV or V) were included in this study. Thirty-six patients (plate group) were operated using the intramedullary nail fixation assisted by lateral monocortical locking plate, and forty-one patients (cable group) were using the intramedullary nail fixation assisted by cables. The clinical information and demographic results were collected and compared. RESULTS: Operation time of plate group was shorter than cable group and the Incisions length of plate group was longer. The fluoroscopy times were 22.8 ± 8.2 in plate group and 33.0 ± 9.0 in cable group (p < 0.01). Compared with the cable group, patients in plate group used less cerclage cables (p < 0.01). Patients in the plate group has less medial cortex displacement compared with the cable group. (p = 0.038). As for the angular difference of neck shaft angle between operated hip and uninjured hip, plate group has less difference compared with the cable group. Time to union was 14.2 ± 3.1 weeks in plate group which is shorter than the cable group (17.9 ± 4.8 weeks). In terms of follow up period, number of malunion, Harris hip score, walking ability and traumatic hip rating scale, no significant differences were detected. CONCLUSIONS: Our results suggest that using lateral monocortical plate as an auxiliary way may have a longer surgical incision and more intraoperative blood loss, however, the operation time is shorter, the fluoroscopy times is less, and the time to union is shorter. Intramedullary nail fixation assisted by lateral monocortical locking plate may be a new option for patients with complex subtrochanteric femur fractures.

Irisin promotes fracture healing by improving osteogenesis and angiogenesis.

Background: Osteogenesis and angiogenesis are important for bone fracture healing. Irisin is a muscle-derived monokine that is associated with bone formation. Methods: To demonstrate the effect of irisin on bone fracture healing, closed mid-diaphyseal femur fractures were produced in 8-week-old C57BL/6 mice. Irisin was administrated intraperitoneally every other day after surgery, fracture healing was assessed by using X-rays. Bone morphometry of the fracture callus were assessed by using micro-computed tomography. Femurs of mice from each group were assessed by the three-point bending testing. Effect of irisin on osteogenic differentiation in mesenchymal stem cells in vitro was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), alkaline phosphatase staining and alizarin red staining. Angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by qRT-PCR, migration tests, and tube formation assays. Results: Increased callus formation, mineralization and tougher fracture healing were observed in the irisin-treated group than in the control group, indicating the better fracture callus healing due to Irisin treatment. The vessel surface and vessel volume fraction of the callus also increased in the irisin-treated group. The expression of BMP2, CD31, and VEGF in callus were enhanced in the irisin-treated group. In mouse bone mesenchymal stem cells, irisin promoted ALP expression and mineralization, and increased the expression of osteogenic genes, including OSX, Runx2, OPG, ALP, OCN and BMP2. Irisin also promoted HUVEC migration and tube formation. Expression of angiogenic genes, including ANGPT1, ANGPT2, VEGFb, CD31, FGF2, and PDGFRB in HUVECs were increased by irisin. Conclusion: All the results indicate irisin can promote fracture healing through osteogenesis and angiogenesis. These findings help in the understanding of muscle-bone interactions during fracture healing. The Translational Potential of this Article: Irisin was one of the most important monokine secreted by skeletal muscle. Studies have found that irisin have anabolic effect one bone remodeling through affecting osteocyte and osteoblast. Based on our study, irisin could promote bone fracture healing by increasing bone mass and vascularization, which provide a potential usage of irisin to promote fracture healing and improve clinical outcomes.

Bone Marrow Mesenchymal Stem Cell Exosome Attenuates Inflammasome-Related Pyroptosis via Delivering circ_003564 to Improve the Recovery of Spinal Cord Injury.

Bone marrow mesenchymal stem cell (BMSC) is previously reported to present a certain effect on treating spinal cord injury (SCI), while the underlying mechanism is largely uncovered. Therefore, the current study aimed to investigate the involvement of exosome-delivered circRNA profile in the BMSC's effect on pyroptosis for SCI treatment. H2O2 treated rat primary neurons were cultured with normal medium, BMSC, BMSC plus GW4869, and BMSC-derived exosome, respectively, then inflammasome-related pyroptosis markers, and circRNA profiles were detected. Subsequently, circ_003564-knockdown BMSC exosome was transfected into H2O2 treated rat primary neurons and NGF-stimulated PC-12 cells. Furthermore, in vivo validation was conducted. BMSC and BMSC-derived exosome both decreased inflammasome-related pyroptosis markers including cleaved caspase-1, GSDMD, NLRP3, IL-1ß, and IL-18 in H2O2-treated neurons, while exosome-free BMSC (BMSC plus GW4869) did not obviously reduce these factors. Microarray assay revealed that BMSC (vs. exosome-free BMSC) and BMSC-derived exosome (vs. normal medium) greatly regulated circRNA profiles, which were enriched in neuroinflammation pathways (such as neurotrophin, apoptosis, and TNF). Among three functional candidate circRNAs (circ_015525, circ_008876, and circ_003564), circ_003564 was most effective to regulate inflammasome-related pyroptosis. Interestingly, circ_003564-knockdown BMSC exosome showed higher expression of inflammasome-related pyroptosis markers compared to negative-control-knockdown BMSC exosome in H2O2 treated primary neurons/NGF-stimulated PC-12 cells. In vivo, BMSC exosome improved the function recovery and decreased tissue injury and inflammasome-related pyroptosis in SCI rats, whose effect was attenuated by circ_003564 knockdown transfection. BMSC exosome attenuates inflammasome-related pyroptosis via delivering circ_003564, contributing to its treatment efficacy for SCI.

MiR-487b suppressed inflammation and neuronal apoptosis in spinal cord injury by targeted Ifitm3.

Spinal cord injury (SCI) was a serious nerve injury, which involves complex genetic changes. This paper was intended to investigate the function and mechanism of differentially expressed genes in SCI. The three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database were used to identify differentially expressed genes (DEGs). We identified the common DEGs in the three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database. Next, a protein-protein interaction (PPI) network of DEGs was constructed. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in immune response, inflammatory response. The expression level of immune-related genes (Arg1, Ccl12, Ccl2, Ifitm2, Ifitm3, and et al.) at different time points of SCI were analyzed in GSE189070 dataset. Next, differentially expressed miRNAs (DE-miRNAs) were identified in SCI compared with normal based on GSE158194 database. DE-miRNA and targeted immune-related genes were predicted by miRwalk, including miR-487b-5p targeted Ifitm3, miR-3072-5p targeted Ccl3, and et al. What's more, the miR-487b was identified and verified to be down-regulated in Lipopolysaccharide (LPS)-induced BV-2 cell model. Further, the miR-487b inhibited cell inflammation and apoptosis in LPS-induced BV2 cell by targeted Ifitm3. For the first time, our results revealed that miR-487b may play an important regulatory role in SCI by targeted Ifitm3 and provide further evidence for SCI research.

Peptidomics Analysis Reveals Serum Biomarkers in Spinal Cord Injury Patients.

Spinal cord injury (SCI) is a severe traumatic disease, always resulting in neuronal injury. In this study, we aimed to exhibit a peptidome profile of serum from patients with SCI. A label-free peptidomics strategy was used to analyze the differentially expressed peptides (DEPs). Then, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses was used to evaluate the function of the peptides precursors proteins. Also, the protein-protein interaction networks were mapped using STRING database. Finally, parallel reaction monitoring assays were used to validate the expression of candidate peptides. We identified 217 DEPs including 29 upregulated peptides and 188 downregulated peptides in SCI group. Many pathways such as Platelet activation, Complement and coagulation cascades, Focal adhesion were enriched. Seven peptides including PSPRPSP, RPPGFSP, DKPDMAEIEKFDKSKLK, STTAVVTNPKE, GHAGAQGPPGPPG, SMPPAQQQITS and SKVLPIQDNVSK were significantly changed between SCI patients and healthy people. Peptidomics provide a powerful tool to find the variation of SCI. RPPGFSP, DKPDMAEIEKFDKSKLK and SMPPAQQQITS may play important roles in SCI. However, the specific function of these peptides and whether they can be used as therapeutic targets for SCI need to be further investigated.

Postoperative Pneumonia in Geriatric Patients With a Hip Fracture: Incidence, Risk Factors and a Predictive Nomogram.

Objectives: To evaluate the incidence and risk factors of postoperative pneumonia (POP) in geriatric patients with a hip fracture after surgery, to design a predictive nomogram, and to validate the accuracy of the nomogram. Design: Retrospective study. Setting: A tertiary hospital affiliated to a medical university. Patients/Participants: We retrospectively studied 1285 surgical-treated geriatric patients with a hip fracture from April 2010 to April 2018. Intervention: Surgical treatment was performed on the patients of this study. The procedure methods were classified as: total hip arthroplasty, hemiarthroplasty, percutaneous fixation, intramedullary nail fixation, and plate/screw fixation. Main Outcome Measurement: The primary interest of end point of this study is the development of POP during the postoperative period. The postoperative period in this study was defined as the time from 24 hours after surgery to discharge. The diagnostic criteria for pneumonia were set according to the guidelines built by the Infectious Diseases Society of America and the American Thoracic Society (Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia, 2005). Potential variables for developing POP were identified using logistic regression analyses initially and were further selected via the method of LASSO. Then the independent risk factors were identified by multivariable regression analyses. A predictive nomogram was built based on the multiple regression model, and the calibration abilities of the nomogram was measured by Harrel C-index, calibration plot and Hosmer-Lemeshow test, respectively. Decision curve analysis was carried out to assess the net benefit due to threshold probability and an on-line questionnaire survey was conducted among the clinicians to assess the applicability of the nomogram coherently. Results: Of the 1285 patients, 70 (5.4%) developed POP. COPD, number of comorbidities, ASA classification >2, preoperative dependent functional status and cognitive impairment were identified as independent risk factors of POP. The nomogram built based on the results showed good accordance between the predicted probabilities and the observed frequency. The decision curve analysis confirmed the clinical utility of the nomogram when the threshold probabilities were between 5% and 65% due to the net benefit, while the results of on-line questionnaire among 200 clinicians showed that 91.5% of the participants had a mental threshold of intervention between 5-50%. Conclusion: (1). COPD, number of comorbidities, ASA classification >2, preoperative dependent functional status and cognitive impairment are independent risk factors for POP. (2). The nomogram built in this study has a good accordance between the predictive risk and the observational incidence. The results of decision curve and questionnaire among clinicians show well applicability of the nomogram.

Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84.

Spinal cord injury (SCI) is a traumatic disease resulting in neuronal injury. circRNAs are closely associated with human diseases. Nevertheless, the potential mechanism by which circRNAs impact SCI remains to be elucidated. The aim of this study was to investigate the regulatory roles of Circular RNAs (circRNAs) in SCI. The SCI mouse model and integrated bioinformatics analysis were used to identify the differentially expressed genes (DEGs). Functional enrichment analysis was conducted to study the related pathways. The circRNA-mediated ceRNA network and subnetwork was constructed based on circMir, TargetScan and miRanda. qRT-PCR, ELISA, flow cytometry, and luciferase reporter assays were carried out to validate the role of circ_0014637 (circ-Usp10) and microRNA(miR)-152-5p /CD84 in microglia. In all, 23 DE-circRNAs, 127 DE-miRNAs and 1327 DE-mRNAs were identified. We integrated these DEGs to construct a circRNA-miRNA-mRNA network. The circ-Usp10/miR-152-5p/CD84 axis was found to function in microglial activation. We also found that circ-Usp10 inhibited the secretion of proinflammatory factors in microglial BV2 cells. In addition, silencing circ-Usp10 significantly reduced the death of the neuronal cell line HT22. Taken together, we concluded that circ-Usp10 may function as a competing endogenous RNA (ceRNA) to promote microglial activation and induce neuronal death by targeting miR-152-5p/CD84. The circ-Usp10 may be a diagnostic biomarker and potential target for SCI therapy.

Intramedullary nails in combination with reconstruction plate in the treatment of unstable intertrochanteric femoral fractures with lateral wall damage.

BACKGROUND: The unstable intertrochanteric femur fracture remains a challenge for surgeons. However, few studies have compared the clinical effectiveness of intramedullary nail in combination with a reconstruction plate and intramedullary nail alone in the treatment of patients with unstable intertrochanteric femoral fractures with lateral wall damage. METHODS: This study retrospectively analyzed 16 patients with 31 A3 intertrochanteric fractures treated with the intramedullary nail in combination with reconstruction plate (the study group) and 19 patients with 31 A3 intertrochanteric fractures treated with intramedullary nail alone (the control group) between January 2012 and January 2018. The operation time, intra-operative blood loss, time of fracture healing, and complication rates of post-operative fixation failure were assessed between the two groups. At the follow-up of post-operative six and 12 months, Harris hip score (HHS) and the Parker-Palmer mobility score (PPMS) were used to evaluate the functional states and mobility levels. RESULTS: The distribution of all basic characteristics was similar between the two groups (P ˃ 0.05). The study group had longer operation time and more intra-operative blood loss in comparison with the control group (P < 0.001), while the study group had shorter fracture healing time (P = 0.03) and lower fixation failure rate as compared with the control group. Regarding the functional outcome, the study group had higher HHSs and PPMS than the control group (P = 0.003). CONCLUSIONS: Although intramedullary nails in combination with reconstruction plates had longer operation time and more intra-operative blood loss, it might be superior to intramedullary nail alone in terms of fracture healing time, fixation failure complication rate, and post-operative functional recovery.

Risk factors for and predictive nomogram of postoperative hypoxaemia in elderly patients with femoral neck fractures.

OBJECTIVE: To investigate the related risk factors and predictive nomogram of postoperative hypoxaemia in elderly patients with femoral neck fractures. METHODS: This study included patients aged ≥65 years who underwent surgical treatment of acute femoral neck fractures. Univariate and multivariate logistic analyses were performed to determine the incidence of and risk factors for postoperative hypoxaemia. A predictive nomogram was constructed based on the multivariable model. Using the bootstrap method, discrimination was determined by the C-index and calibration plot. RESULTS: The logistic regression analysis showed that the anaesthesia type, surgical procedure, American Society of Anesthesiologists (ASA) classification, preoperative hypoxaemia occurrence, and age were independent predictors of development of postoperative hypoxaemia. The predictive formula for hypoxaemia was established as follows: hypoxaemia=-0.8668×spinal anaesthesia (whether)+0.1162×nerve anaesthesia (whether)+1.9555×plate/screw fixation (whether)+1.4950×hip replacement (whether)+0.4883×ASA classification+1.7153×preoperative oxygenation index+0.1608×age. With the bootstrap method, the prediction curve fit well with the ideal curve, suggesting that the prediction curve constructed in this study has good predictive ability. CONCLUSIONS: Anaesthesia type, surgical procedure, ASA classification, preoperative hypoxaemia occurrence, and age were risk factors for postoperative hypoxaemia in elderly patients with femoral neck fractures. The predictive nomogram was designed for preoperative assessment of the risk of postoperative hypoxaemia by calculating the risk score.

Delayed surgery versus nonoperative treatment for hip fractures in post-COVID-19 arena: a retrospective study of 145 patients.

Background and purpose - Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods - In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results - Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24-48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation - In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications.

Hidden blood loss after hip hemiarthroplasty using the superPATH approach: A retrospective study.

OBJECTIVE: The purpose of this study was to compare perioperative hidden blood loss after hip hemiarthroplasty via the SuperPATH approach and the conventional posterior approach (the Moore approach). PATIENTS AND METHODS: From January 2015 to January 2017, 130 patients (80.7 ±â€¯6.0 years) with displaced femoral neck fracture (Garden type III or IV) undergoing hip hemiarthroplasty were included in this study. As a non-randomisation study, Fifty-two patients (SuperPATH group) were operated using the SuperPATH approach, and 78 patients (Moore group) were operated with the conventional posterior approach (Moore approach). The demographic and relevant clinical information of the patients were collected. According to the combination formulas of Nadler, Gross and Sehat, the hidden blood loss (HBL) of each patient was calculated. Student's t-test for independent samples was used to compare the normally distributed variables and the Mann-Whitney U test was used to compare variables not following a normal distribution. RESULTS: The visible blood loss (VBL) in the SuperPATH group was 123.7 ±â€¯47.5 ml, the hidden blood loss (HBL) was 1084.1 ±â€¯816.8 ml and the HBL% was 82.7 ±â€¯16.5%. In the Moore group, the VBL was 303.6 ±â€¯139.6 ml, the HBL was 700.2 ±â€¯563.8 ml and the HBL% was 61.5 ±â€¯23.8%. The patients in the SuperPATH group had more HBL and HBL% (P < 0.05). However, no significant difference was observed of total blood loss (TBL) between the two groups (P = 0.125). CONCLUSIONS: HBL should not be ignored in patients who underwent hip hemiarthroplasty for displaced femoral neck fractures, as it is a significant portion of TBL. Compared with the conventional approach, the SuperPATH approach had a greater amount of HBL. A better understanding of HBL after hip hemiarthroplasty may help surgeons improve clinical assessment and ensure patient safety.

Predictive nomogram for postoperative delirium in elderly patients with a hip fracture.

To evaluate the risk factors for the development of postoperative delirium and design a predictive nomogram for the prevention of delirium in elderly patients with a hip fracture, we retrospectively studied 825 patients who sustained a femoral neck fracture from January 2005 to December 2015. Independent risk factors for developing delirium within 6 months of surgery were identified using multivariable logistic regression analyses. A predictive nomogram model was built based on the results, and the discrimination and calibration were determined by C-index and calibration plot. Of the 825 patients who met inclusion criteria, 118 (14.3%) developed postoperative delirium. According to the results, preoperative cognitive impairment (OR, 4.132, 95% CI, 1.831 to 9.324, P＜0.001), multiple medical comorbidities (OR, 1.452, 95% CI, 0.958-2.202, P = 0.079), ASA classification (OR, 1.655, 95% CI, 1.073-2.553, P = 0.023), transfusion exceeding 2 units of red blood cell (OR, 1.599, 95% CI, 1.043-2.451, P = 0.035), and intensive care (OR, 1.817, 95% CI, 1.127-2.930, P = 0.014) were identified to be the independent predictors of the development of postoperative delirium. The risk of postoperative delirium increased with the increasing risk score of predictive nomogram, and the C-index was 0.67 (0.62 - 0.72). The calibration showed that the predicted probabilities of delirium in the predictive nomogram were close to the observed frequency of delirium, and the decision curve analysis confirmed the clinical utility of the nomogram when the threshold probabilities were between 8% and 35% due to the net benefit.

A new less invasive surgical technique in the management of acute Achilles tendon rupture through limited-open procedure combined with a single-anchor and "circuit" suture technique.

BACKGROUND: Traditional incision repair and minimally invasive repair for acute Achilles tendon repair have limitations. This study aimed to present our series of 23 patients with acute Achilles tendon rupture that was repaired using two small incisions to assist the anchor repair of the tear and a new "circuit" suture technique. METHODS: This was a retrospective study of 23 patients with acute Achilles tendon rupture treated with the new technique at Changhai Hospital between January 2015 and December 2016 and followed up for 14-33 months. Clinical outcome was assessed using the AOFAS, Leppilahti, and Arner-Lindholm scores. Complications, range of motion (ROM), and time to return to work and light sport activity were assessed. RESULTS: The AOFAS score was 85-96 at 3 months and 92-100 at 12 months. The 3-month ROM was 27°-37°, and the 12-month ROM was 36°-48°. The Leppilahti score was 85-95 at 3 months and 90-100 at 12 months. The recovery time of the patients was 10-18 weeks. The postoperative recovery time to exercise was 16-24 weeks. There was only one case of deep venous thrombosis. According to the Arner-Lindholm assessment criteria, patient outcomes were rated as excellent in 20 (87.0%) cases, good in three (13.0%) cases, and poor in 0 cases. The excellent-to-good rate was 100%. CONCLUSION: The limited-open procedure combined with a single-anchor and "circuit" suture technique could be used to repair torn Achilles sites, with a low occurrence of complications. This new and minimally invasive technique could be an alternative in the management of acute Achilles tendon rupture.

[Manipulative reduction and plaster external fixation for the treatment of the scaphoid fracture and perilunate dislocation].

OBJECTIVE: To investigate the efficacy and complications of manual reduction and external fixation for the treatment of scaphoid fractures and perilunate dislocations. METHODS: From January 2009 to January 2013, 43 patients suffered from scaphoid fractures and perilunate dislocations were retrospective analyzed. Among them, 17 cases were treated with manipulative reduction and plaster external fixation as conservation group including 10 males and 7 females, the other 26 cases were treated with application of surgical as operation group including 15 males and 11 females. The clinical effects were assessed by Cooney function score, radiological analysis and observation of complications. RESULTS: All patients were followed up for(45.00±8.72) months ranging from 36 to 60 months. At the final follow-up, the Cooney score of wrist function was 88.53±4.24 in conservation group and 89.58±4.59in operation group(t=0.455, P>0.05). During the follow-up, 4 patients were found scaphoid avascular necrosis in the imaging performance in the conservation group(χ²=4.32, P<0.05). The difference of other complications between two groups was not statistically significant(P>0.05). CONCLUSIONS: For patients suffered from the scaphoid fractures and perilunate dislocation, the early manipulative reduction and plaster external fixation after injury as soon as possible is necessary. Maintaining a satisfactory reduction and reliable fixation at the same time can lead to good treatment effect and there's no weakness compared to surgical treatment. But there was an increase in danger of complications. The key of conservative treatment lies in early diagnosis and maintenance of reduction, reliable fixation, and timely and appropriate functional exercise.

Macrophage polarization, inflammatory signaling, and NF-κB activation in response to chemically modified titanium surfaces.

Functionalization of titanium devices with various bioactive molecules enhances many of their properties as implants, including biocompatibility, which is typically assessed by macrophage activation and inflammation. However, functionalization requires prior introduction of reactive groups, to which bioactive agents can then be grafted. Thus, we investigated the inflammatory properties of titanium pretreated with NaOH, titanium pretreated with NaOH and then with 3-aminopropyl triethoxysilane, and titanium pretreated with dopamine. Inflammation, macrophage polarization, and activation of NF-κB signaling were assessed by real-time PCR and western blotting. The data demonstrate that silanized titanium is the least inflammatory, and promotes macrophage M2 polarization with modest engagement of the NF-κB signaling pathway. Importantly, silanization introduces a reactive amino group, providing more opportunities for further functionalization.

miR-422a inhibits osteosarcoma proliferation by targeting BCL2L2 and KRAS.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. However, the underlying mechanism of osteosarcoma carcinogenesis and progression remains unknown. In the present study, we evaluated the expression profile of miRNAs in osteosarcoma tissues and the adjacent normal tissues. We found that the expression of miR-422a was down-regulated in osteosarcoma tissues and cell lines. In addition, we observed significantly elevated levels of repressive H3K9me3 and H3K27me3 and decreased active H3K4me3 on the promote region of miR-422a in osteosarcoma cells and clinical samples. Furthermore, up-regulation of miR-422a exhibited both in vitro and in vivo anti-tumor effects by inhibiting osteosarcoma cell growth and inducing apoptosis and cell cycle arrest. We also found that miR-422a targeted BCL2L2 and KRAS and negatively regulated their protein expression. Furthermore, restoration of miR-422a and knockdown of BCL2L2 and KRAS promoted apoptosis and induce cell cycle arrest in osteosarcoma cells. Taken together, the present study demonstrates that miR-422a may serve as a tumor suppressor in osteosarcoma via inhibiting BCL2L2 and KRAS translation both in vitro and in vivo Therefore, miR-422a could be developed as a novel therapeutic target in osteosarcoma.

Vancomycin-loaded titanium coatings with an interconnected micro-patterned structure for prophylaxis of infections: an in vivo study.

Titanium (Ti) and its alloys are widely applied as orthopedic implants for hip and knee prostheses, fixation, and dental implants. However, Ti and its alloys are bioinert and susceptible to bacteria and biofilm formation. Thus, surface biofunctionalisation of Ti is essential for improving the biofunction of Ti. The current in vitro study indicated that calcium phosphate bone cement with vancomycin doped on micro-patterned Ti with a grid-like structure surface could preserve the property of inhibition of bacterial adhesion and biofilm formation while not affecting the osteogenic differentiation. The present study investigated whether the biological performance of the bactericidal effect is preserved in vivo. The rabbit osteomyelitis model with tibial medullary cavity placement of Ti rods was employed to analyze the antibacterial effect of vancomycin-loaded Ti coatings with interconnected micro-patterned structure (TV). Thirty female rabbits (N = 10) were used to establish the implant-associated infection. Prior to implanting the T0 and TV rods into the medullary cavity of the left tibia of the rabbits, 106 CFU mL-1 methicillin-resistant Staphylococcus aureus (MRSA) was injected into the medullary cavity of the left tibia of the rabbits. The sterile Ti rod (NT) was used as the blank control. After 3 weeks, bone pathology was evaluated using X-ray and micro-CT. The in vivo study proposed that TV has the potential for prophylaxis against MRSA infection. Thus, the interconnected micro-patterned structured Ti rods loaded with vancomycin could be applied for preventing Ti implant-associated infections.

Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression.

Deregulated expression of circular RNA (circRNA) has been determined to be important in carcinogenesis and progression; however, in the most common type of primary malignant bone tumor osteosarcoma, the roles of circRNA in cancer development still remain to be elucidated. Here, we found that circRNA UBAP2 (circUBAP2) expression is significantly increased in human osteosarcoma tissues as compared to those in matched controls. Increased circUBAP2 expression was significantly correlated with human osteosarcoma progression and prognosis. Furthermore, increased circUBAP2 could promote osteosarcoma growth and inhibit apoptosis both in vitro and in vivo. Mechanistically, circUBAP2 was found to inhibit the expression of microRNA-143 (miR-143), thus enhancing the expression and function of anti-apoptotic Bcl-2, which is a direct target of miR-143. Together, our results suggest the roles of circUBAP2 in osteosarcoma development and implicate its potential in prognosis prediction and cancer therapy.

miR-106a-5p Suppresses the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Targeting HMGA2.

We aim to investigate the effect of miR-106a-5p on the proliferation, migration, and invasion of osteosarcoma (OS) cells by targeting high-mobility group AT-hook 2 (HMGA2). Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used for detecting the expressions of miR-106-5p and HMGA2 in 137 OS and adjacent normal bone tissues. Immunohistochemistry was applied for the HMGA2 protein expression detection. Luciferase reporter gene assay was conducted for verifying whether miR-106-5p targeted HMGA2. MG63 and U2SO cells were respectively divided into five groups: Blank, miR-106a-5p, scramble, HMGA2-siRNA, and miR-106a-5p+HMGA2 groups. RT-qPCR and western blot were applied for detecting the expressions of miR-106a-5p and HMGA2 in five groups. Proliferation rate, cell cycle, invasion, and migration ability of OS cells were detected using methyl thiazolyl-tetrazolium, 5-ethynyl-2'-deoxyuridine (Edu) assay, flow cytometry, and Transwell. Compared with adjacent normal tissues, OS tissues presented with decreased miR-106a-5p expressions, elevated HMGA2 mRNA, and positive expressions (all p < 0.05). The sensitivity and specificity of miR-106a-5p were 97.8%, 93.43%, and HMGA2 mRNA were 97.8%, 99.27%, separately. miR-106a-5p and HMGA2 expressions were associated with tumor size, Enneking stage, distant metastasis, and lung metastasis. Expressions of HMGA2 in OS cells in miR-106a-5p and HMGA2 siRNA groups were both significantly decreased with the same downregulation level, and the proliferation rates in both groups were obviously slowed down after 48 h (both p < 0.001). Edu positive cells, S phase cells (majority of cells blocked at G0/G1 phase), migratory and invasive cells were obviously decreased (all p < 0.05). Downregulation of miR-106a-5p was found in OS tissues, and upregulation of miR-106a-5p can inhibit the proliferation, migration, and invasion by targeting HMGA2 in OS cells.