Circular RNA IARS modulates the progression and ferroptosis of osteosarcoma via sponging miR-188-5p from RAB14.

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.

Mechanisms of Ferroptosis-Related Genes in Gallbladder Cancer Based on Bioinformatics Analysis.

Gallbladder Cancer (GBC) is a lethal malignancy with limited treatment options and poor prognosis. Recent studies have emphasized the role of ferroptosis, a regulated form of cell death, in various cancers, including GBC. We applied bioinformatics methodologies on four GBC datasets to identify differentially expressed genes (DEGs). An intersection of DEGs from the four datasets with ferroptosis and GBC-associated genes was done to identify key ferroptosis-related genes in GBC. GSVA pathway enrichment analysis and immune cell infiltration assessment were conducted to explore their functional roles and interactions. Seven ferroptosis-related genes, EZH2, MUC1, PVT1, GOT1, CDO1, LIFR, and TFAP2A, were identified to be related to GBC. These genes were associated with vital signaling pathways like the G2/M checkpoint and DNA repair and showed significant correlations with immune cell infiltration in GBC. Receiver Operating Characteristic (ROC) curve analysis revealed their high diagnostic potential, with Area Under the Curve (AUC) values ranging from 0.796 to 0.953. Our findings underscore the pivotal role of ferroptosis in GBC and the potential of ferroptosis-related genes as diagnostic biomarkers. This study lays a foundation for further research into ferroptosis-based therapeutic strategies for GBC.

Inhibition of ZDHHC16 promoted osteogenic differentiation and reduced ferroptosis of dental pulp stem cells by CREB.

BACKGROUND: The repair of bone defects caused by periodontal diseases is a difficult challenge in clinical treatment. Dental pulp stem cells (DPSCs) are widely studied for alveolar bone repair. The current investigation aimed to examine the specific mechanisms underlying the role of Zinc finger DHHC-type palmitoyl transferases 16 (ZDHHC16) in the process of osteogenic differentiation (OD) of DPSCs. METHODS: The lentiviral vectors ZDHHC16 or si-ZDHHC16 were introduced in the DPSCs and then the cells were induced by an odontogenic medium for 21 days. Subsequently, Quantitate Polymerase Chain Reaction (PCR), immunofluorescent staining, proliferation assay, ethynyl deoxyuridine (EdU) staining, and western blot analysis were used to investigate the specific details of ZDHHC16 contribution in OD of DPSCs. RESULTS: Our findings indicate that ZDHHC16 exhibited a suppressive effect on cellular proliferation and oxidative phosphorylation, while concurrently inducing ferroptosis in DPSCs. Moreover, the inhibition of ZDHHC16 promoted cell development and OD and reduced ferroptosis of DPSCs. The expression of p-CREB was suppressed by ZDHHC16, and immunoprecipitation (IP) analysis revealed that ZDHHC16 protein exhibited interconnection with cAMP-response element binding protein (CREB) of DPSCs. The CREB suppression reduced the impacts of ZDHHC16 on OD and ferroptosis of DPSCs. The activation of CREB also reduced the influences of si-ZDHHC16 on OD and ferroptosis of DPSCs. CONCLUSIONS: These findings provide evidences to support a negative association between ZDHHC16 and OD of DPSCs, which might be mediated by ferroptosis of DPSCs via CREB.

Outcomes that may affect implant and prosthesis survival and complications in maxillary fixed prosthesis supported by four or six implants: A systematic review and meta-analysis.

Objective: To investigate whether the clinical and radiographical outcomes are affected when four or six implants support the maxillary fixed complete denture (FCD). Materials and methods: This study was registered on PROSPERO (CRD42021226432) and followed the PRISMA guidelines. The focused PICO question was, "For an edentulous maxillary patient rehabilitated with an implant-supported fixed prosthesis, do the clinical and radiographical outcomes differ when four or six implants support the prosthesis ". A thorough search of the relevant studies was designed and performed electronically. The survival rate of implant and prosthesis, marginal bone loss, and complications (mechanical and biological) were the primary outcomes, whereas implant distribution and using the surgical guide, follow-up, and framework material were evaluated as secondary outcomes. Results: Out of 1099 articles initially retrieved, 53 clearly stated the outcomes of interest and were included in this study. There were no significant differences in implant and prosthesis survival, technical/mechanical complications, and biological complications between the 4-implant group (4-IG) and the 6-implant group (6-IG). However, marginal bone loss (MBL) was significantly higher in the 4-IG (p < 0.01). The surgical guide and follow-up period did not significantly affect implant/prosthesis survival. Additionally, using the CAD/CAM milled framework and anteroposterior implant distribution were associated with significantly higher implant survival in the 6-IG (p < 0.01). Conclusion: The findings of this study indicated that having a greater number of implants, as seen in the 6-implant group, can lead to a decrease in technical and biological complications and reduce marginal bone loss. It is worth noting that factors such as using CAD/CAM frameworks and the anteroposterior distribution of implants were recognized as important in improving implant survival rates when more implants are present.

The biofilm removal effect and osteogenic potential on the titanium surface by electrolytic cleaning: An in vitro comparison of electrolytic parameters and five techniques.

OBJECTIVES: To determine the optimal current and time of electrolytic cleaning (EC), compare its biofilm removal effect with generic treatments and evaluate the influence of EC to surface characteristics and osteogenic potential of SLA titanium (Ti) discs. MATERIALS AND METHODS: The six-species biofilm-covered Ti discs were placed as cathodes in physiologic saline and subjected to various current and time treatments. The residual biofilms were evaluated to determine the optimal parameters. The contaminated Ti discs were randomized and treated by rotating Ti brush; ultrasonic-scaling with metal tips; ultrasonic-scaling with PEEK tips; air-polishing and EC. The residual biofilms were compared using a lipopolysaccharide kit (LPS), scanning electron microscope (SEM), confocal laser scanning microscopy and colony-forming unit counting. Non-contaminated Ti discs were treated and characterized. The bone marrow mesenchymal stem cells (BMSCs) were cultured on treated non-contaminated Ti discs. The adhesion, proliferation, alkaline phosphatase (ALP) activity and osteocalcin level of BMSCs were assessed. RESULTS: The parameters at 0.6A5min were considered optimal. For LPS and SEM, EC promoted a significantly greater biofilm removal than the other groups. There were no changes in the Ti discs' colour, topography, roughness and chemical elements after EC, and the electrolysis-treated Ti discs obtained a super-hydrophilic surface. EC positively impacted the proliferation and ALP activity of BMSCs, surpassing the efficacy of alternative treatments. CONCLUSIONS: EC achieves a near-complete eradication of contaminants on the SLA surface, causes no surface damage with improved hydrophilicity, and promotes the early osteogenic response of BMSCs, which makes it a promising treatment for peri-implantitis.

Long-term outcome of flexor hallucis longus tendon transfer for chronic Achilles tendon rupture with large defect: A retrospective series.

There are multiple surgical options for treatment of chronic Achilles tendon (AT) rupture according to the classifications and length of defect. However, no gold standard method has been confirmed, and there is no clear evidence to support the superiority of 1 procedure over others. This study aimed to evaluate the long-term clinical outcome of flexor hallucis longus tendon (FHL) transfer for chronic AT rupture with large defect. Clinical data of patients treated with FHL transfer due to chronic AT rupture between January 2009 and October 2019 were reviewed retrospectively. All cases were presented with AT rupture for more than 4 weeks after injury. The gap between ruptured ends was > 5 cm after debridement in all patients. The harvest of FHL was performed through a single incision in accordance with AT rupture debridement in all cases. Clinical outcomes were assessed with AOFAS ankle-hindfoot scale, Achilles tendon total rupture score and AOFAS hallux metatarsophalangeal-interphalangeal scale. Twenty-eight patients were followed successfully for 62.6 ±â€…22.2 months. According to the complete datasets obtained from 28 patients, none of the tendons re-ruptured. The AOFAS ankle-hindfoot scale and Achilles tendon total rupture score at last follow-up visit was 90.4 ±â€…5.7 and 89.8 ±â€…5.3 respectively, which revealed statistically significant improvement from the preoperative score of 61.1 ±â€…6.7 and 53.8 ±â€…8.3. The AOFAS hallux metatarsophalangeal-interphalangeal scale at last follow-up visit was 87.5 ±â€…6.1. The FHL transfer through a single incision for chronic AT rupture with large defect is a safe and simple method with low risk of morbidity and complications.

Titanium surface interacting with blood clot enhanced migration and osteogenic differentiation of bone marrow mesenchymal stem cells.

Introduction: Blood clot formation is the initial phase upon implantation, and the feature of blood clot orchestrates the following complement system activation, coagulation cascade, and bone marrow mesenchymal stromal cells (BMSCs) recruitment. This study aimed to investigate the effect of implant surface on blood-material interactions and subsequent BMSC cellular behaviors. Methods: This study was established to imitate the physiological process of implantation in vivo and in vitro. Whole blood was incubated with polished titanium (PT) surfaces and sandblasted and double acid-etching (SLA) surfaces for 10 min or 2 h, then seeded with BMSCs. The adhesion, proliferation, migration, and differentiation of cells were studied at specific time points. Titanium implants were implanted into the tibia in vivo and were screwed out after implantation. The activation of the coagulation cascade, platelets, complement system, and clot networks were assessed and further quantitatively analyzed. Results: Compared with the PT surface, the SLA surface induced the earlier and stronger blood coagulation cascade and formed a more stratified clots network with fibrinogen, platelets, and CD14 positive cell. The adhesion, proliferation, and migration of BMSCs were enhanced by pre-incubated surfaces. The higher levels of the osteogenic-related genes, ALP activity, and calcium nodule formation were showed on SLA surfaces with blood incubation. Conclusion: SLA titanium surfaces play a role in influencing the formation of blood clots and coordinating surface-blood interactions and cell biological processes. These findings provide the idea of modifying the blood clots formed on the implant surface by biomaterials modification and thus has implications for the development of better osteogenic biomaterials.

Risk factors associated with loss of variable-thread tapered implants: A retrospective observational study of 1-5 years.

OBJECTIVES: This study aimed to evaluate the survival rate of variable-thread tapered implants (VTTIs) and identify risk factors for early/late implant loss. MATERIALS AND METHODS: From January 2016 to December 2019, patients who received VTTIs were included in this study. The cumulative survival rates (CSRs) at implant/patient levels were calculated by the life table method and presented via Kaplan-Meier survival curves. The relation between investigated variables and early/late implant loss was analyzed by the multivariate generalized estimating equation (GEE) regression model on the implant level. RESULTS: A total of 1528 patients with 2998 VTTIs were included. 95 implants from 76 patients were lost at the end of observation. At the implant level, the CSRs at 1, 3, and 5 years were 98.77%, 96.97%, and 95.39%, respectively, whereas they were 97.84%, 95.31%, and 92.96% at the patient level, respectively. The multivariate analysis revealed that non-submerged implant healing (OR = 4.63, p = .037) was associated with the early loss of VTTIs. Besides, male gender (OR = 2.48, p = .002), periodontitis (OR = 3.25, p = .007), implant length <10 mm (OR = 2.63, p = .028), and overdenture (OR = 9.30, p = .004) could significantly increase the risk of late implant loss. CONCLUSION: Variable-thread tapered implants could reach an acceptable survival rate in clinical practice. Non-submerged implant healing was associated with early implant loss; male gender, periodontitis, implant length <10 mm, and overdenture would significantly increase the risk of late implant loss.

IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.

BACKGROUND: The biomaterial integration depends on its interaction with the host immune system. Monocyte-macrophage lineage cells are immediately recruited to the implant site, polarized into different phenotypes, and fused into multinucleated cells, thus playing roles in tissue regeneration. IL-1R-associated kinase 4 (IRAK4) inhibition was reported to antagonize inflammatory osteolysis and regulate osteoclasts and foreign body giant cells (FBGCs), which may be a potential target in implant osseointegration. METHODS: In in-vitro experiments, we established simulated physiological and inflammatory circumstances in which bone-marrow-derived macrophages were cultured on sand-blasted and acid-etched (SLA) titanium surfaces to evaluate the induced macrophage polarization, multinucleated cells formation, and biological behaviors in the presence or absence of IRAK4i. Then, bone marrow stromal stem cells (BMSCs) were cultured in the conditioned media collected from the aforementioned induced osteoclasts or FBGCs cultures to clarify the indirect coupling effect of multinucleated cells on BMSCs. We further established a rat implantation model, which integrates IRAK4i treatment with implant placement, to verify the positive effect of IRAK4 inhibition on the macrophage polarization, osteoclast differentiation, and ultimately the early peri-implant osseointegration in vivo. RESULTS: Under inflammatory conditions, by transforming the monocyte-macrophage lineage cells from M1 to M2, IRAK4i treatment could down-regulate the formation and activity of osteoclast and relieve the inhibition of FBGC generation, thus promoting osteogenic differentiation in BMSCs and improve the osseointegration. CONCLUSION: This study may improve our understanding of the function of multinucleated cells and offer IRAK4i as a therapeutic strategy to improve early implant osseointegration and help to eliminate the initial implant failure.

Marginal bone loss of tissue- or bone-level implants after simultaneous guided bone regeneration in the posterior mandibular region: A retrospective cohort study.

PURPOSE: To analyze the marginal bone loss (ΔMBL) of tissue- or bone-level implants after placed with simultaneous guided bone regeneration (GBR). MATERIALS AND METHODS: A total of 151 patients who received 104 tissue-level or 128 bone-level implants placement with simultaneous GBR in the mandibular posterior region between January 2011 and December 2016 were included in this study. The marginal bone level (MBL) was recorded using the radiographic data obtained at implant placement, second-stage surgery, and the follow-up visit. Generalized estimating equation (GEE) was used to compare the ΔMBL of tissue- and bone-level implants, and the influencing factors of ΔMBL were further analyzed. RESULTS: At the last follow-up visit, the MBL of tissue-level implants was 0.73 ± 0.86 mm, above the rough-smooth interface, while that of bone-level implants was 0.82 ± 1.05 mm, above the implant platform. The ΔMBL of tissue-level implants was 1.03 mm, which was slightly higher than 0.81 mm of bone-level implants, but there was no significant difference (p > 0.05). No contributing factor associated with ΔMBL was identified by multivariate regression analysis in this study. CONCLUSION: Within the limits of this retrospective analysis, the ΔMBL of tissue-level implants is similar to that of bone-level implants after placed with simultaneous GBR, and both types of implants can achieve desirable marginal bone stability.

Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.

Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems. The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive. Here, a single-cell study involving 40043 cells is conducted, and a total of 10 distinct cell clusters are identified from five different groups. A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties. The increased immature neutrophils, Ly6C + CCR2hi monocytes, and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant. The enrichment of mature neutrophils, FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response. Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration. Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis. These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of 'osteoimmune-smart' biomaterials in the bone regeneration field.

Analysis of implant loss risk factors after simultaneous guided bone regeneration: A retrospective study of 5404 dental implants.

PURPOSE: The purpose was to analyze the risk factors for implant loss after simultaneous guided bone regeneration (GBR). MATERIALS AND METHODS: Patients who underwent implant placement with simultaneous GBR between January 2011 and December 2018 were screened for this study. The cumulative survival rate (CSR) was calculated using the life table method. Log-rank test and Kaplan-Meier survival estimates were used to identify potential risk factors for implant loss. The association between the investigated variables and implant loss was determined using hazard ratios (HRs) obtained from a multivariate Cox regression analysis. RESULTS: A total of 3973 patients with 5404 implants were included in this study. The CSRs of the implants at 1, 5, and 10 years were 99.6%, 98.9%, and 98.7%, respectively. Male patient (HR = 2.94, 95% CI: 1.41-6.14), periodontitis (HR = 4.26, 95% CI: 2.05-9.86), tissue-level implants (HR = 3.02, 95% CI: 1.30-6.98), narrow implants (HR = 2.71, 95% CI: 1.12-6.57), and implant length ≤10 mm (HR = 2.91, 95% CI: 1.41-6.02) significantly increased the risk of implant loss (p < 0.05). The risk of implant loss was significantly higher in the maxillary posterior region (HR = 2.26, 95% CI: 1.04-4.90) than in the maxillary anterior region (p < 0.05). Compared to Straumann, Nobel (HR = 4.07, 95% CI: 1.75-9.44) and other implant systems (HR = 14.23, 95% CI: 4.32-46.85) showed a significantly higher risk of implant loss (p < 0.05). CONCLUSION: Male patient, periodontitis, maxillary posterior region, Nobel implant system, other implant systems, tissue-level implants, narrow implants, and implant length ≤10 mm were considered risk factors for implant loss after simultaneous GBR.

Local administration of epsilon-aminocaproic acid reduces post-operative blood loss from surgery for closed, Sanders III-IV calcaneal fractures.

PURPOSE: To investigate whether local administration of epsilon-aminocaproic acid (EACA) is effective and safe in reducing the post-operative blood loss in surgery for Sanders III-IV calcaneal fractures. METHODS: Patients with Sanders III-IV calcaneal fractures who were hospitalized in our hospital from January 2016 to February 2021 and underwent open reduction internal fixation (ORIF) via lateral approach with an L-shaped incision were included in the current study. Eighty five patients were randomly divided into two groups, EACA group (43) and control group (42). Twenty milliliters of 5% EACA solution or normal saline was perfused into the incision of patients in EACA group and control group, respectively. The volume of post-operative drainage was investigated as the primary outcome. Post-operative blood test, coagulation test, and wound complications were analyzed as the secondary outcomes. RESULTS: The volume of post-operative drainage at 24 and 48 h was 164.8 ± 51.4 ml, 18.9 ± 3.8 ml for patients in EACA group, and 373.0 ± 88.1 ml, 21.2 ± 4.4 ml for patients in the control group, respectively. EACA greatly reduced the post-operative blood loss compared to the control (normal saline). The difference between the two groups was statistically significant. No statistically significant difference was found between EACA group and control group with regard to the pre-operative, baseline characteristics. Post-operative blood test results demonstrated that haemoglobin and hematocrit were significantly higher in EACA compared to those of control group. No significant difference was found between EACA group and control group in terms of the platelet counts, prothrombin time (P.T.), activated partial prothrombin time (APTT), and wound complications. CONCLUSION: Local administration of EACA is effective in post-operative blood loss reduction in ORIF surgeries for Sanders III-IV types of calcaneal fractures without increasing the incidence of periwound complication.

iTRAQ-based proteomic analysis reveals potential osteogenesis-promoted role of ATM in strontium-incorporated titanium implant.

The present study aims to reveal the osteogenic roles played by DNA damage response biomarkers through implementing isobaric tags for relative and absolute quantitation (iTRAQ) technique. First, sandblasted large-grit double acid-etched (SLA) titanium implant and strontium-incorporated (SLA-Sr) titanium implant were used for inserting in the tibiae of rats. iTRAQ technique was used to detect protein expression changes and identify differentially expressed proteins (DEPs). In total, 19,343 peptides and 4280 proteins were screened out. Among them, 91 and 138 DEPs were identified in the SLA-Sr group after implantation for 3 and 7 days, respectively. Ataxia-telangiectasia mutated (ATM) protein up-regulated on the 3rd day showed a trend of further up-regulation on the 7th day. Moreover, functional enrichment analyses were also conducted to explore the biological function of DEPs during the initial stage of osseointegration in vivo, which revealed that the biological functions of the DEPs on the 7th day were mainly related to "mismatch repair" and "mitotic G1 DNA damage checkpoint." Analysis of the Reactome signaling pathway showed that ATM was associated with TP53's regulation and activation. Finally, DNA damage repair related genes were selected for validation at mRNA and protein expression levels. Real-time reverse transcription-polymerase chain reaction and immunohistochemistry validation results demonstrated that mRNA expression level of ATM was higher in SLA-Sr group. In conclusion, SLA-Sr titanium implant could initiate DNA damage repair by activating expression levels of ATM. This study was striving to reveal new faces of better osseointegration and shedding light on the biological function and underlying mechanisms of this important procedure.

Modulating autophagy by strontium-doped micro/nano rough titanium surface for promotion of osteogenesis and inhibition of osteoclastogenesis.

Although it has been demonstrated that implant surfaces treated with strontium (Sr) promote osseointegration, the underlying intracellular mechanism remains unknown. Autophagy is a vital intracellular degradation mechanism that plays an essential role in maintaining bone homeostasis. Therefore, while designing implant biomaterials, it is critical to consider the autophagy mechanism. In this study, we fabricated Sr-doped micro/nano rough titanium implant surface by hydrothermal treatment (SLA+Sr). The in vitro results revealed that the SLA+Sr surface promoted osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via autophagy activation. The SLA+Sr surface, on the other hand, inhibited osteoclast differentiation by downregulating autophagy. Additionally, in vivo, the SLA+Sr implant improved osseointegration, inhibited osteoclastogenesis, and upregulated autophagy levels in surrounding bone tissue cells. Our findings established a novel centralized mechanism by which SLA+Sr regulated osteogenesis and osteoclastogenesis during the osseointegration process through autophagy regulation. Moreover, endowing implants with the ability to modulate autophagy may be a promising strategy for enhancing implant osseointegration in the future translational medicine field.

TGF-ß protects osteosarcoma cells from chemotherapeutic cytotoxicity in a SDH/HIF1α dependent manner.

BACKGROUND: In the widespread adoption of chemotherapy, drug resistance has been the major obstacle to tumor elimination in cancer patients. Our aim was to explore the role of TGF-ß in osteosarcoma-associated chemoresistance. METHODS: We performed a cytotoxicity analysis of methotrexate (MTX) and cisplatin (CIS) in TGF-ß-treated osteosarcoma cells. Then, the metabolite profile of the core metabolic energy pathways in Saos-2 and MG-63 cell extracts was analyzed by 1H-NMR. We detected the expression of succinate dehydrogenase (SDH), STAT1, and hypoxia-inducible factor 1α (HIF1α) in TGF-ß-treated osteosarcoma cells and further tested the effects of these molecules on the cytotoxicity induced by chemotherapeutic agents. Using in vivo experiments, we examined the tumor growth and survival time of Saos-2-bearing mice treated with a combination of chemotherapeutic agents and a HIF1α inhibitor. RESULTS: The metabolic analysis revealed enhanced succinate production in osteosarcoma cells after TGF-ß treatment. We further found a decrease in SDH expression and an increase in HIF1α expression in TGF-ß-treated osteosarcoma cells. Consistently, blockade of SDH efficiently enhanced the resistance of Saos-2 and MG-63 cells to MTX and CIS. Additionally, a HIF1α inhibitor significantly strengthened the anticancer efficacy of the chemotherapeutic drugs in mice with osteosarcoma cancer. CONCLUSION: Our study demonstrated that TGF-ß attenuated the expression of SDH by reducing the transcription factor STAT1. The reduction in SDH then caused the upregulation of HIF1α, thereby rerouting glucose metabolism and aggravating chemoresistance in osteosarcoma cells. Linking tumor cell metabolism to the formation of chemotherapy resistance, our study may guide the development of additional treatments for osteosarcoma.

Strontium-incorporated titanium implant surfaces treated by hydrothermal treatment enhance rapid osseointegration in diabetes: A preclinical vivo experimental study.

OBJECTIVES: The aim of the current study was to explore effects of strontium-incorporated titanium implant surfaces by hydrothermal treatment on osseointegration in diabetic rats. MATERIALS AND METHODS: The surface characteristics of SLA and SLA-Sr surfaces were detected by related instruments. Thirty-six male Sprague-Dawley rats were induced into diabetes, and thirty-six rats were normal. SLA and SLA-Sr implants were, respectively, inserted into bilateral tibial metaphysis of each rat. Percentage of bone-to-implant contact (BIC%) and percentage of bone area (BA%) were analyzed at 4 and 8 weeks after implantation. Immunohistochemistry of osteoprotegerin (OPG) and Wnt5a were conducted at 1 and 4 weeks. Gene expression levels of inflammatory cytokines and related signaling molecules in peri-implant bone tissue were detected at 3 and 7 days. RESULTS: Strontium was uniformly distributed on SLA-Sr surfaces, and it was released in an effective concentration range. SLA-Sr surfaces showed significantly higher BIC% in diabetic rats at 4 (p < .05) and 8 weeks (p < .05). Besides, it displayed higher BIC% at 4 weeks (p < .05) in normal rats. Also, SLA-Sr surfaces upregulated expression of OPG at 4 weeks (p < .05) in diabetic rats. What's more, SLA-Sr surfaces downregulated inflammation (TNF-α, IL-1ß, and IL-6; p < .01) in diabetic rats at 3 days. In addition, expression of Wnt5a and ROR2 was upregulated (p < .05) at 7 days after implantation under diabetes. CONCLUSION: It is suggested that strontium-incorporated titanium implant surfaces by hydrothermal treatment could enhance implant osseointegration as compared with SLA implant surfaces in diabetic rats.

Secondary below-knee amputation following open reduction and internal fixation of a closed pilon fracture: A case report and algorithm for management.

RATIONALE: Despite significant advances in surgical techniques and implants, the clinical outcome of high-energy pilon fractures remains unsatisfactory, which continues to represent numerous challenges for orthopedic trauma surgeons. PATIENT CONCERNS: A 62-year-old man injured his right ankle after falling from a 3 m high place. There were no open wounds or other complications. DIAGNOSES: According to the X-ray and CT scans, the patient was diagnosed with pilon fracture (type AO-43-C2) and lateral malleolus fracture of the right limb. INTERVENTIONS: The patient was initially treated with calcaneal traction upon admission to a primary hospital. Five days after the injury, the patient underwent open reduction and internal fixation (ORIF) of the fracture and vacuum sealing drainage (VSD) for wound closure. OUTCOMES: The patient presented to our hospital on the 9th day after the first ORIF operation because of critical ischemia of the affected foot and distal lower leg. Blood circulation did not improve after a series of salvage treatments, and below-knee amputation was ultimately performed. LESSONS: This is a rare case of complete ischemic necrosis following ORIF surgery of a closed pilon fracture due to iatrogenic damage. Standardized treatment that strictly follows the guidelines, instructions, or expert consensus should be promoted in this kind of complicated pilon fracture.

Codelivery of survivin inhibitor and chemotherapeutics by tumor-derived microparticles to reverse multidrug resistance in osteosarcoma.

Reportedly, the elevated expression of survivin has been observed in several tumor types, strictly involved in tumor development. In the present study, we detected elevated survivin expression in tumor tissues derived from patients with chemoresistant osteosarcoma when compared with those from chemosensitive patients. Importantly, knockdown of survivin in osteosarcoma cells significantly suppressed cell proliferation and chemoresistance both in vitro and in vivo. Simultaneously, chemotherapy mediates the upregulation of survivin in osteosarcoma cells through a survivin-based selective killing effect, resulting in the development of multidrug resistance. The utilization of tumor-derived microparticles to coencapsulate the survivin inhibitor YM155 and chemotherapeutic agents could effectively reverse multidrug resistance, leading to improved anticancer effects, as well as reduced systemic toxicity. In summary, the expression of survivin contributes to resistance toward osteosarcoma drugs, whereas employing survivin inhibiting combination therapy, based on a microparticle codelivery system, could efficiently reverse resistance and avoid potential systemic toxicity.

Comparing less invasive plate fixation versus screw fixation of displaced intra-articular calcaneus fracture via sinus tarsi approach.

PURPOSE: The purpose of this study was to compare the post-operative radiographic and clinical outcomes of less invasive plate fixation versus screw fixation of displaced intra-articular calcaneus fractures (DIACFs) via sinus tarsi approach. METHODS: A total of 165 consecutive DIACFs that underwent open reduction internal fixation via sinus tarsi approach from 2013 to 2018 were reviewed at least a two year follow-up. The methods of fixation were divided into two groups: less invasive plate fixation versus screw fixation of calcaneus fracture (59 vs 106, respectively). The radiographic outcomes including pre- and post-operative Bohler's and Gissane's angles were evaluated. The post-operative function was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, the Olerud and Molander Scale and the Visual Analogue Scale (VAS). The complications, the rates of implant removal and cost were also compared. RESULTS: The average follow-up was 44.2 months in the plate groups and 47.9 months in the screw groups (P > 0.05). There was no significant difference in the Bohler's angle and Gissane's angle between the plate group and screw group during the pre-operation and the last follow-up. There was no significant difference in the final AOFAS score, Olerud and Molander score and VAS score between the two groups (P > 0.05). The total incidence of complications was 6.7% in the plate group and 6.6% in the screw group (P > 0.05). The rates of implant removal and total cost during the hospitalization in the plate group were significantly higher compared with screws group (P < 0.05). CONCLUSION: The less invasive plate fixation versus screw fixation of DIACFs via sinus tarsi approach contributed comparable quality of reduction, complications and post-operative functional outcomes. The less invasive plate technique was significantly higher in terms of implant costs and the rate of implant removal.