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Purpose To evaluate whether the 24-weeks postoperative fracture union rate for the investigational TFNA intramedullary nail was non-inferior compared to the control product PFNA-II. Methods The study was a prospective, randomized, single-blind, noninferiority dual-arm study drawing from 9 trauma centers across China, between November 2018 and September 2020, with follow-up measurements at 24 weeks after internal fixation. The full analysis data set (FAS [Intent-to-Treat]) was analyzed and is summarized here. The primary outcome was fracture union rate, a composite score combining clinical and radiographic assessment. Secondary endpoints comprised (a) clinical outcomes including (1) SF-12, (2) Harris Hip, and (3) EQ-5D Scores, (b) radiographic incidence of complications such as loosening or cut-out requiring revision, (c) revision rates, (d) reoperation rates, and (e) adverse events, including 24-weeks revision and reoperation rates. Results Both TFNA and PFNA-II group fracture healing rates were 100% at 24 weeks; TFNA was therefore shown to be non-inferior to PFNA-II. With baseline data matched in all parameters except age in both the TFNA and PFNA-II groups, comparisons of union rates, SF-12, Harris Hip, and EQ-5D Scores yielded p values > 0.05 indicating no significant difference between the two groups, further supporting the noninferiority of TFNA. In both groups, revision and re-operation rates were 0, and the incidences of serious adverse events were 19.4% and 17.4%, respectively. Conclusion In terms of fracture union rate at 24 weeks, the DePuy Synthes Trochanteric Fixation Nail Advanced (TFNA) was not inferior to the marketed Proximal Femoral Nail Antirotation (PFNA-II) device produced by the same manufacturer. Secondary and safety outcomes showed no significant differences between the two groups. Registration Registration was completed at ClinicalTrials.gov NCT03635320.

Osteoarthritis (OA), the commonest arthritis type, features irreversible cartilage loss and synovitis. It was reported that macrophages have an important function in synovial inflammation, and our team revealed that the amounts of Sirt6, a nicotinamide adenine dinucleotide (NAD)

Background Multiple disruptions of the superior shoulder suspensory complex (SSSC) involving more than two components are extremely rare. In some extreme situations, three components of the SSSC structure can be involved. The ideal treatment for this type of injury is debatable. Case presentation A 21‐year‐old woman was referred to our emergency center following a traffic accident. A three‐dimensional CT scan showed triple disruption of the SSSC involving concomitant ipsilateral fractures of the coracoid, the acromion, and the distal clavicle. The connection between the upper limber and the axial skeleton was destroyed. There was no evidence of associated injury and the neurovascular examination of the injured upper limb was normal. The patient underwent an open reduction and internal fixation to restore the anatomic integrity of the SSSC. The arm was supported in a broad arm sling for 2 weeks after surgery. Gentle passive range of motion activity under analgesic was encouraged from the second day postoperatively. One year and half after the operation, the patient had regained pain free and unrestricted shoulder stability and mobility. Conclusion The manifestations of multiple disruptions of the SSSC may be variable. This case illustrated the challenges of treating the multiple disruption of the SSSC structure. It also showed that surgical intervention for this rare combination injury yields an excellent functional result. The good outcome achieved in this patient demonstrates that surgical intervention might be an optional resolution for multiple disruptions of the SSSC., The SSSC is a ring of bone and soft tissue, which is composed of the coracoclavicular ligament, the distal clavicle, the AC joint, the coracoacromial ligament and the acromion, the coracoid process, and the glenoid. We presented a case of a triple bone break of this ring.

Objective To gain a better understanding of the traumatic mechanism and to develop appropriate treatment for dislocation of the shoulder joint with an ipsilateral humeral shaft fracture. Methods This was an observational and descriptive study. Nine patients with traumatic shoulder dislocations associated with ipsilateral humeral shaft fractures who visited the emergency room and received treatment from January 2012 to June 2018 were retrospectively analyzed. CT with three‐dimensional reconstruction was performed to provide precise anatomical information of the fractures. The traumatic event and the type of fracture of the humeral shaft were analyzed to help determine the trauma mechanism. Closed reduction of the dislocation was attempted at once under intravenous anesthesia. One patient died the following day due to unrelated causes. All humeral shaft fractures of the eight patients received internal fixation, and then reduction of the dislocation was performed again if previous attempts failed. The affected limb was immobilized in a sling for 3 weeks postoperatively, and then active and passive movement was encouraged. Patients were evaluated based on clinical and radiographic examinations, shoulder joint range of motion, Constant–Murley score, and subjective shoulder value. Results Four cases in the present study could not give a clear description of the traumatic procedure. The other five patients suffered a second strike on their upper arms when they were hurt, with low mobility and high pain in the shoulder region. Seven cases were simple fractures and two were wedge fractures. According to the AO/OTA classification system, four cases were type 12‐A2, three were type 12‐A3, and two were type 12‐B2. Six patients successfully obtained closed manipulative reduction of the shoulder dislocation in the acute stage. The follow‐up time ranged from 18 to 31 months. No deep wound infections were encountered. All fractures healed uneventfully. The union time ranged from 4 to 6 months. At the final follow‐up, shoulder range‐of‐motion values were found to range from 140° to 170° forward flexion, 30° to 40° extension, 40° to 45° adduction, 150° to 170° abduction, 50° to 60° internal rotation, and 50° to 60° external rotation; no recurrent instability of the shoulder joint occurred; the Constant–Murley score was 89.5 ± 3.7 points (range: 84–94 points); the subjective shoulder value was 89.4% ± 6.3% (range: 75%–95%). Conclusion Shoulder dislocation most likely occurs first with an axial force or a direct posteroanterior force and a subsequent force results in the shaft fracture. For patients with mid‐distal humerus fractures, closed manipulative reduction of the joint is usually effective. After success of closed reduction, surgery for the humeral shaft fracture is advocated to ensure stability and to make patient nursing convenient. In cases with fractures in the proximal third of the humeral shaft, fixation is suggested beforehand to help reduce the shoulder dislocation., To describe a treatment strategy for shoulder dislocation associated with a concomitant ipsilateral humeral shaft fracture.

Summary: Bone metabolism depends on the balance between osteoclast-driven bone resorption and osteoblast-mediated bone formation. Diseases like osteoporosis are characterized by increased bone destruction due to partially enhanced osteoclastogenesis. Here, we report that the post-translational SUMO modification is critical for regulating osteoclastogenesis. The expression of the SUMO-specific protease SENP3 is downregulated in osteoclast precursors during osteoclast differentiation. Mice with SENP3 deficiency in bone marrow-derived monocytes (BMDMs) exhibit more severe bone loss due to over-activation of osteoclasts after ovariectomy. Deleting SENP3 in BMDMs promotes osteoclast differentiation. Mechanistically, loss of SENP3 increases interferon regulatory factor 8 (IRF8) SUMO3 modification at the K310 amino acid site, which upregulates expression of the nuclear factor of activated T cell c1 (NFATc1) and osteoclastogenesis. In summary, IRF8 de-SUMO modification mediated by SENP3 suppresses osteoclast differentiation and suggests strategies to treat bone loss diseases. : Osteoclast over-activation leads to osteoporosis, but the role of post-translational modification in osteoporosis is not fully understood. Zhang et al. show that the SUMO protease SENP3 can alter the SUMO modification status on the critical osteoclast suppressor IRF8 in osteoclast precursor cells, which affects osteoclastogenesis and osteoporosis. Keywords: SENP3, osteoclastogenesis, SUMOylation, osteoporosis

Objective To evaluate clinical and radiological outcomes of proximal femoral nail anti-rotation (PFNA-II) devices and demonstrate the effectiveness of PFNA-II for the treatment of basicervical fractures in elderly patients. Methods A retrospective review of all patients treated with PFNA-II for a proximal femoral fracture between January 2013 and February 2017 at three different institutions (Shanghai General Hospital, Shanghai Punan Hospital and Shanghai Seventh People's Hospital) was conducted. The X-ray films were strictly reviewed by three trauma surgeons and a professional radiology doctor. Patients over 60 years of age who met the following criteria were included: (i) sustained low-energy trauma; (ii) a two-part fracture; (iii) fracture line located at the base of the femoral neck and that was medial to the intertrochanteric line and exited above the lesser trochanter but was more lateral than a classic transcervical fracture. Follow-up time should be longer than 6 months. A total of 52 patients who met the inclusion criteria were selected. The average age at diagnosis was 75.1 years (range, 63-91 years); 13 patients were men and 39 were women. The same proximal femoral nail anti-rotation devices and the same surgical procedures were applied to all patients. Postoperative radiographic union time and modified Harris hip scores were used as major indicators for evaluating the effectiveness of surgery. Results The average follow-up period was 22.5 months (18.5, 23.9, and 21.2 months, respectively) and radiographic unions were observed at an average of 19.6 weeks (range, 12-28 weeks). The patients were evaluated immediately after surgery, as well as 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Of the 49 patients, 38 had good reduction qualities (75.5%), 9 acceptable (18.3%), and 3 poor (6.1%). Radiographic union was confirmed in all fractures at an average of 19.6 weeks (range, 12-28 weeks). The mean Harris hip score was 84.9 (range, 65-99): excellent in 9 patients (18.36%), good in 30 (61.22%), medium in 8 (16.32%), and poor in 2 (4.08%). Slight persistent pain occurred in 3 patients, but these patients could still walk with the help of a cane. Two patients had symptoms of excessive telescoping. Eight patients experienced postoperative medical complications, mainly pneumonia and urinary tract infection. Conclusion Based on the clinical and radiological outcomes, the PFNA-II devices provide strong rotational stability and excellent clinical prognosis, and are an appropriate treatment option for basicervical proximal femoral fracture in elderly patients.

To ensure a timely response to emergencies, governments are obliged to implement effective ambulance allocation plans. In practice, an emergency medical service (EMS) system works in an uncertain environment, with stochastic demand, response-times, and travel-times. This uncertainty significantly affects ambulance allocation planning. However, few studies in this field adequately consider the effect of spatiotemporal uncertainty in demand, because it is difficult to measure it quantitatively. As a result, few analytic models capture the dynamic nature of an EMS system and, thus, the allocation plans they generate are not efficient in practice. Therefore, this study proposes a simulation-based optimization method for ambulance allocation. A simulation model is constructed to mimic the operational processes of an EMS system, and to evaluate the performance of an ambulance allocation plan in an uncertain environment. Gaussian mixture model clustering is used to derive the uncertain spatial demand. Then, the simulation generates emergency demand based on the obtained spatial distribution. A Gaussian-process-based search algorithm is used together with the simulation model to identify optimal solutions. To validate the proposed method, a case study is conducted using data on emergency patients in the Shanghai Songjiang District. Compared with the current plan adopted in Songjiang, the experimental results demonstrate that the delay time and frequency of the EMS system can be reduced significantly by employing the proposed methods. Furthermore, nearly 41% of the allocation cost can be saved.

Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite. Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.

To radiographically characterize the relationship between inferior displacement of great tuberosity (GT) fracture and associated occult or minor displaced humeral neck fracture. Thirty patients with inferior displacement of the GT on the initial anterior-posterior (AP) view X-ray were included in this study. Twenty-four patients received further computed tomography (CT) scans. One patient with negative CT scans underwent MRI. Radiographic indexes included the cervico-diaphyseal angle, the distance of the inferior displacement of the GT fracture, the apex-tuberosity distance, and the direction of the GT shift on the 3D-CT scan. The measurement reliability was analyzed by calculating intra-class correlation (ICC) coefficients. The relationships between the parameters were revealed using Pearson correlation analysis. In the 30 cases, humeral neck fractures were detected by AP view X-ray (6 cases), CT (23 cases), and MRI (1 case). The mean cervico-diaphyseal angle was 146.7° ± 8.9°. The mean inferior displacement of the GT fracture was 13.4 ± 5.9 mm. The mean apex-tuberosity distance was 11.8 ± 2.8 mm. Posterior/inferior displacement of the GT fractures was observed in 24 patients via CT scan. All the evaluated parameters presented correlations among methods, indicating intra-rater and inter-rater reliability. The Pearson correlation analysis revealed that inferior displacement of GT fracture was correlated with the cervico-diaphyseal angle (P

Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We orally exposed AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al could induce bone damages, bone loss and oxidative stress. In addition, we showed that Al triggered inflammatory responses, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN treatment significantly alleviated Al-induced bone injuries by decreasing bone loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively, our results suggest that NMN may reduce Al-induced bone loss partly by suppression of the TXNIP-NLRP3 inflammasome pathway.

Acetabular fractures are a real challenge for junior doctors as well as experienced orthopedic surgeons. Correct fracture classification is crucial for appreciating the fracture type, surgical planning, and predicting prognosis. Although three-dimensional (3D) tutorial is believed to improve the understanding of the complex anatomy structure, there have been few applications and randomized controlled trials to confirm it in orthopedics. This study aims to develop a 3D interactive software system for teaching acetabular fracture classification and evaluate its efficacy. Participants were randomly but evenly allocated into either the experimental group (who learned the acetabular fracture classification using a 3D software) or the control group (who used a traditional two-dimensional [2D] tutorial). Both groups were then tasked to classify 10 acetabular fractures and complete a five-point Likert scale on their satisfaction of each learning modality. To calculate significance (P < 0.05), independent t-test was used for normally distributed data whereas Mann-Whitney U test for non-normally distributed data. The experimental group significantly outperformed the control group (t (28) = 2.526, P = 0.017) with identifying correct acetabular fracture classification. Moreover, Likert scale score in the experimental group was also significantly higher than in the control group (Z = 2.477, P = 0.013). This 3D classification software has objectively and subjectively showed an advantage over the traditional 2D tutorial, resulting in an improved classification accuracy and higher Likert scale score. The 3D software has the potential to improve both clinical knowledge as well as identifying correct patient management in orthopedics.

In this work, multifunctional polystyrene@chitosan@gold nanoparticles-Fe

Objective: To investigate the innovative application of gold nanorods combined with a laser in posttraumatic osteoarthritis (PTOA) modeling and to discuss the possible mechanisms. Methods: Electron microscopy was used to characterize the gold nanorods. Cell counting kit-8 assay and enzyme-linked immunosorbent assay were used to evaluate cell proliferation and cytotoxicity. An infrared spectroscopy (IR) thermal camera was used to monitor the temperature changes of gold nanorods with or without the laser treatment. Furthermore, western blotting was used to evaluate the expression of related proteins in response to the indicated treatments. Finally, microcomputed tomography (micro-CT) was used to determine the structural changes in knee joints. Changes in the cartilage and various other tissues were assessed by histological examination. Results: The characteristics and biosafety of the gold nanorods were confirmed. Our study showed that gold nanorods combined with the laser inhibited cell viability, but the gold nanorods or laser alone did not affect cell viability. Moreover, the effect on cell viability was time dependent. Similarly, only gold nanorods with the laser caused the apoptosis of cartilage cells and the upregulation of IL-1β, MMP-13 and Comp. We injected gold nanorods and used laser irradiation to develop an osteoarthritis (OA) model. The temperature of the knees in the OA model increased to 60 °C and then remained at approximately 60 °C. As the time increased, gold nanorods combined with the laser caused more injuries and degeneration in the knee joints. Conclusion: OA models that were established using gold nanorods and a laser were precise, controllable, observable and stable and could be an excellent premise for investigating the exact mechanisms underlying OA and exploring new treatment strategies.

Pubic symphysis diastasis with an incidence of approximately 20% in pelvic fractures is a severe lesion which needs to be treated properly. The objective of this retrospective study was to describe and evaluate the clinical and radiological outcomes including its advantages and limitations of this modified minimal invasive technique. Totally 29 patients with pubic symphysis diastasis, with or without posterior ring instability, were treated by modified pedicle screw–rod fixation (modified PSRF) between January 2010 and December 2016. The duration from injury to surgery, operation time, intraoperative blood loss as well as complications were recorded. During follow-up, the functional outcomes were assessed according to the Majeed evaluation criteria 1 year postoperatively. The evaluation of the postoperative reduction quality was carried out according to Matta criteria. According to Tile classification, there were 9 cases of Type B1 underwent only anterior-modified PSRF and 20 cases of Type C1 experienced anterior-modified PSRF combined with posterior fixation. The duration from injury to operation, operation time and intraoperative blood loss were 3.27 days (range 1–6 days), 42.07 min (range 38–45 min), and 46.14 ml (range 40–55 ml). The results of reduction quality were rated as excellent in 16, good in 11 and fair in 2 based on Matta criteria. The Majeed functional scores ranged from 68 to 95 and there were excellent in 15, good in 12 and fair in 2. No patients experienced incision infection. Slight loosening of middle-two screws was verified during follow-up in one patient. Two patients underwent femoral nerve palsy. Irritation to the LFCN was detected in four patients. Modified PSRF can be performed as an alternative to manage pubic symphysis diastasis due to its merits of minimal invasive, less blood loss, less soft tissue injuries as well as shorter operation time, even with the early weight-bearing. Researchregistry3905.

Recently, accumulating evidence demonstrated that the long non-coding RNAs (lncRNAs) play important roles in osteoarthritis (OA) progression. However, the role of lncRNA FOXD2-AS1 on OA is still unclear. In the present study, qRT-PCR showed that expression of FOXD2-AS1 and Cyclin D1 (CCND1) was upregulated in OA cartilage tissues, while miR-206 expression was significantly decreased. CCK-8 and colony formation assays showed that FOXD2-AS1 could promote chondrocytes viability. Flow cytometry analysis showed that FOXD2-AS1 inhibition arrested chondrocytes in G0/G1 phase and induced cells apoptosis. Furthermore, luciferase reporter assay and RIP assay showed that FOXD2-AS1 could function as a sponge of miR-206. Rescue assays showed that miR-206 inhibitors reversed the effects of FOXD2-AS1 suppression on chondrocytes viability. In addition, we identified that CCND1 acted as a direct target of miR-206. FOXD2-AS1 suppression could inhibit CCND1 expression in chondrocytes, while miR-206 inhibitors reversed CCND1 expression. Moreover, rescue assays indicated that CCND1 overexpression reversed the effects of FOXD2-AS1 suppression on chondrocytes viability. Taken together, these data indicated that FOXD2-AS1 could promote the growth of chondrocytes by targeting miR-206/CCND1 axis.

The objective of this study was to develop and validate a novel 3D dynamic model of a pelvic side-impactor system. The biomechanical responses of a pelvic flexible model (having .mnf file suffix) under the lateral impact load for predicting the bone fracture mechanism are investigated as well. The 3D solid model of the side-impactor system was imported into MSC/ADAMS software for analyzing the dynamic model, and the pelvic flexible model was extracted from the CT images of a Chinese female volunteer. The flexible model of the pelvis system was developed considering a wide range of mechanical properties in the bone complex and soft tissue to achieve a realistic biomechanical response during a lateral impact. Good agreements were achieved between the dynamic simulations and the experimental results of pelvic side impacts, in terms of the biomechanical criteria. The dynamic model of impactor system could be employed to investigate the hip protector effectiveness, improving the vehicle safety, and biomechanical response of the other human organs.

The present prospective study examined the utility of the intraoperative tap test/technique for distal tibiofibular syndesmosis in the diagnosis of deltoid ligament rupture and compared the outcomes of transsyndesmotic fixation to deltoid ligament repair with suture anchor. This diagnostic technique was performed in 59 ankle fractures with suspected deltoid ligament injury. The width of the medial clear space of 59 cases was evaluated to assess the sensitivity and specificity. Those with deltoid ligament rupture were randomly assigned to 2 groups and treated with deltoid ligament repair with a suture anchor or with syndesmosis screw fixation. All the patients were assessed with the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, short-form 36-item questionnaire (SF-36), and visual analog scale (VAS). The tap test was positive in 53 cases. However, surgical exploration demonstrated that 51 cases (86.4%) had a combined deltoid ligament injury and fracture. The sensitivity and specificity of the tap test was 100.0% and 75.0%, respectively. Finally, 26 cases (96.3%) in the syndesmosis screw group and 22 (91.7%) in the deltoid repair group were followed up. No statistically significant differences were found in the AOFAS ankle-hindfoot scale score, SF-36 score, or VAS score between the 2 groups. The malreduction rate in the syndesmosis screw group was 34.6% and that in the deltoid repair group was 9.09%. The tap test is an intraoperative diagnostic method to use to evaluate for deltoid ligament injury. Deltoid ligament repair with a suture anchor had good functional and radiologic outcomes comparable to those with syndesmotic screw fixation but has a lower malreduction rate. We did not encounter the issue of internal fixation failure or implant removal.

Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO2 nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO2 nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO2 nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO2. And Se@SiO2 has few interference to the therapeutic effect of DOX. Particularly, Se@SiO2 significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO2 in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO2 nanocomposite in the clinical use of DOX.

The development and design of polymeric hydrogels for articular cartilage tissue engineering have been a vital biomedical research for recent days. Organic/inorganic combined hydrogels with improved surface activity have shown potential for the repair and regeneration of hard tissues, but have not been broadly studied for articular cartilage tissue engineering applications. In this work, bi-polymeric hydrogel composite was designed with the incorporation some quantities of stick-like TiO2 nanostructures for favorable surface behavior and enhancement of osteoblast adhesions. The microscopic investigations clearly exhibited that the stick-like TiO2 nanostructured materials are highly inserted into the PVA/PVP bi-polymeric matrix, due to the long-chain PVA molecules are promoted to physical crosslinking density in hydrogel network. The results of improved surface topography of hydrogel matrixes show that more flatted cell morphologies and enhanced osteoblast attachment on the synthesized nanocomposites. The crystalline bone and stick-like TiO2 nanocomposites significantly improved the bioactivity via lamellipodia and filopodia extension of osteoblast cells, due to its excellent intercellular connection and regulated cell responses. Consequently, these hydrogel has been enhanced the antibacterial activity against Staphylococcus aureus and Escherichia coli bacterial pathogens. Hence it is concluded that these hydrogel nanocomposite with improved morphology, osteoblast behavior and bactericidal activity have highly potential candidates for articular cartilage tissue regeneration applications.

Drug delivery system studies aim to improve nanoparticle (NP) formulation to enable efficient delivery of NPs to tumors. However, NPs must be transported by blood or through direct injection. How NPs leave the circulatory system and how NPs diffuse into a tumor remain unclear, and this uncertainty is a limitation of drug delivery systems. The intimate connection between these questions and metabolism may be related to their biosafety in vivo. Thus, in this study, classical carrier SiO2 NPs were used as typical transport NPs, and fluorescein isothiocyanate (FITC) was used as the representative drug and tracer. As exosome and tunneling nanotubes (TNTs) are the most relevant mechanism for NP transportation and considering the local situation in a tumor, we focused on identifying this phenomenon and investigating TNTs. In conclusion, we effectively demonstrated that NPs can be transferred from cell to cell. Nanotubes may play an important role in this process.

Background: In the field of tissue engineering, there is currently increasing interest in new biomedical materials with high osteogenic ability and comparable mechanical function to repair bone defects. Three-dimensional (3-D) bioactive borosilicate glass (BG) scaffolds exhibit uniform interconnected macro-pores, high porosity and high compressive strength. In this study, we fabricated 3-D BG scaffolds by the 3D printing technique, then coated the surface of the 3-D BG scaffolds with mesoporous bioactive glass (MBG) (BG-MBG scaffold). Methods: The biocompatibility of the BG-MBG scaffolds was evaluated by assessing biodegradability, cell proliferation, alkaline phosphatase (ALP) activity and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of osteogenic gene expression with human bone marrow stromal cells (hBMSCs). Moreover, the BG-MBG scaffolds were used to repair rat femoral defects and their performance was evaluated using microcomputed tomography (micro-CT), fluorescence labeling, histological analysis and immunohistochemical (IHC) analysis. Results: The results showed that the BG-MBG scaffolds possessed ordered nearly 4nm meso-pores and regular macro-pores, as well as good biodegradability, and that they stimulated the proliferation and osteogenic differentiation of hBMSCs. In in vivo studies, the result of micro-CT reconstructed images (BG-9M group, 0.63 ± 0.02 g/cm3 and BG group 0.13 ± 0.02 g/cm3 ) and van Gieson staining (BG-9M groups, 62.67 ± 3.39% and BG group, 12.33 ± 2.58%) showed that the BG-MBG scaffolds could significantly enhance new bone formation in both inner and peripheral scaffolds in defects, in and in without the presence of growth factors or stem cells (P < 0.05). Conclusions: It is believed from these results that the BG-MBG scaffolds possess excellent osteoinductive and osteogenic properties which will make them appealing candidates for bone defect repair. The novelty of our research is to provide a new material to treat bone defects in clinic.

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

The fabella is a kind of sesamoid bone which is located in the lateral head of the gastrocnemius muscle. A slice of studies demonstrated that fabella is involved in the knee joint stabilization. Fabella fracture may cause knee pain or functional impairment as the previous reports pointed. It is extremely rare, which leads to its high rate of missed diagnosis in clinical and radiography to some extent. We report a case of a 38-year-old female who was struck by an electromobile. The fabella fracture was confirmed on X-ray plain films. After that, the degree of injury was evaluated with the magnetic resonance imaging (MRI).

Background The accurate distal locking of intramedullary (IM) nails is a clinical challenge for surgeons. Although many navigation systems have been developed, a real-time guide method with free radiation exposure, better user convenience, and high cost performance has not been proposed. Methods This paper aims to develop an electromagnetic navigation system named TianXuan-MDTS that provides surgeons with a proven surgical solution. And the registration method with external landmarks for IM nails and calibration algorithm for guiders were proposed. A puncture experiment, model experiments measured by 3D Slicer and cadaver experiments (2 cadaveric leg specimens and 6 drilling operations) are conducted to evaluate its performance and stability. Results The registration deviations (TRE) is 1.05± 0.13 mm. In the puncture experiment, a success rate of 96% can be achieved in 45.94 s. TianXuan-MDTS were evaluated on 3 tibia model. The results demonstrated that all 9 screw holes were successfully prepared at a rate of 100% in 91.67 s. And the entry point, end point, and angular deviations were 1.60±0.20 mm, 1.47±0.18 mm, and 3.10±0.84°, respectively. Postoperative fluoroscopy in cadaver experiments showed that all drills were in the distal locking holes, with a success rate of 100% and the average time 143.17± 18.27 s. Conclusions The experimental results indicate that our system with novel registration and calibration methods could serve as a feasible and promising tool to assist surgeons during distal locking.

Acute paraquat (PQ) poisoning is one of the most common forms of pesticide poisoning. Oxidative stress and inflammation are thought to be important mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge intracellular free radicals directly or indirectly. In this study, we investigated whether porous Se@SiO2 nanospheres could alleviate oxidative stress and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells were used in this study. Rats were categorized into 3 groups: control (n=6), PQ (n=18), and PQ + Se@SiO2 (n=18). The PQ and PQ + Se@SiO2 groups were randomly and evenly divided into 3 sub-groups according to different time points (24, 48 and 72 h) after PQ treatment. Porous Se@SiO2 nanospheres 1 mg/kg (in the PQ + Se@SiO2 group) were administered via intraperitoneal injection every 24 h. Expression levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α and interleukin-1β were detected, and a histological analysis of rat lung tissues was performed. The results showed that the levels of ROS, malondialdehyde, NF-κB, p-NF-κB, tumor necrosis factor-α and interleukin-1β were markedly increased after PQ treatment. Glutathione and superoxide dismutase levels were reduced. However, treatment with porous Se@SiO2 nanospheres markedly alleviated PQ-induced oxidative stress and inflammation. Additionally, the results from histological examinations and wet-to-dry weight ratios of rat lung tissues showed that lung damage was reduced after porous Se@SiO2 nanosphere treatment. These data indicate that porous Se@SiO2 nanospheres may reduce NF-κB, p-NF-κB and inflammatory cytokine levels by inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO2 nanospheres may be a therapeutic method for use in the future for PQ poisoning.

To evaluate the clinical outcomes of anterior subcutaneous internal fixator using triple pedicle screws (ASIF/TPS) in the treatment of unstable type B pelvic fracture compared with open reduction internal fixation (ORIF). This was a retrospective cohort study of 26 patients with type B unstable fractures that underwent ASIF/TPS and 26 similar patients that underwent ORIF using plates and screws. Intraoperative blood loss, operating time, and post operation hospitalization duration were compared. Anteroposterior, inlet, and outlet X-rays and 3D computed tomography were obtained. Pain, numbness, sexual dysfunction, and activity were evaluated at every follow-up visit until the implants were removed. The Majeed score was used to assess the clinical and radiological outcomes. Blood loss, operating time, and hospitalization duration were less (all P

Implant placement has been widely used in various kinds of surgery. However, accurate intraoperative drilling performance is essential to avoid injury to adjacent structures. Although some commercially-available surgical navigation systems have been approved for clinical applications, these systems are expensive and the source code is not available to researchers. 3D Slicer is a free, open source software platform for the research community of computer-aided surgery. In this study, a loadable module based on Slicer has been developed and validated to support surgical navigation. This research module allows reliable calibration of the surgical drill, point-based registration and surface matching registration, so that the position and orientation of the surgical drill can be tracked and displayed on the computer screen in real time, aiming at reducing risks. In accuracy verification experiments, the mean target registration error (TRE) for point-based and surface-based registration were 0.31±0.06mm and 1.01±0.06mm respectively, which should meet clinical requirements. Both phantom and cadaver experiments demonstrated the feasibility of our surgical navigation software module.

In this work, multifunctional polystyrene@chitosan@gold nanoparticles-Fe3O4 nanoparticles-folic acid/indocyanine green (PS@CS@Au-Fe3O4-FA/ICG) nanocomposites that can integrate diagnosis and therapy into one nanoplatform was fabricated. The constructed PS@CS@Au-Fe3O4-FA/ICG nanocomposites possessed excellent computed tomography, magnetic resonance and fluorescence imaging performances which could be used to diagnose tumor and monitor the nanocomposites' localization in vivo. Moreover, PS@CS@Au-Fe3O4-FA/ICG nanocomposites can be delivered in a targeted manner to cancer cells by folic acid in a receptor-mediated way, and tumor growth could be efficiently inhibited, even completely ablated, under NIR irradiation. That is, the constructed PS@CS@Au-Fe3O4-FA/ICG nanocomposites had great potential for computed tomography, magnetic resonance and fluorescence imaging performances, which could be used to diagnose tumors and to monitor local therapy and fluorescence imaging-guided targeted therapy of cancer cells using nanocomposites.

Heart disease is one of the most common diseases in the world. The objective of this study is to aid the diagnosis of heart disease using a hybrid classification system based on the ReliefF and Rough Set (RFRS) method. The proposed system contains two subsystems: the RFRS feature selection system and a classification system with an ensemble classifier. The first system includes three stages: (i) data discretization, (ii) feature extraction using the ReliefF algorithm, and (iii) feature reduction using the heuristic Rough Set reduction algorithm that we developed. In the second system, an ensemble classifier is proposed based on the C4.5 classifier. The Statlog (Heart) dataset, obtained from the UCI database, was used for experiments. A maximum classification accuracy of 92.59% was achieved according to a jackknife cross-validation scheme. The results demonstrate that the performance of the proposed system is superior to the performances of previously reported classification techniques.

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

Osteoarthritis (OA) is a common degenerative joint disease worldwide. Long non-coding RNAs (lncRNAs) have been widely confirmed to involve in the modulation of OA progression. However, the underlying mechanisms of lncRNA FOXD2-AS1 in OA remain unclear. In the present study, we showed FOXD2-AS1 expression was upregulated and positively associated with the severity of OA patients. IL-1β and/or TNF-α treatment could increase FOXD2-AS1 expression in chondrocytes. FOXD2-AS1 overexpression induced cell proliferation, inflammation and extracellular matrix (ECM) degradation in chondrocytes. Mechanistically, we found that FOXD2-AS1 upregulated the expression level of TLR4 by sponging miR-27a-3p. In addition, we revealed that miR-27a-3p mimics could abolish the effects of FOXD2-AS1 overexpression on cell proliferation, inflammation, and ECM degradation in chondrocytes. Therefore, we demonstrated that FOXD2-AS1 could play a crucial role in the progression of OA, at least partially, by regulating miR-27a-3p/TLR4 axis.

Deltoid ligament injuries appear with isolated or even no displacement of the lateral malleolus fracture which could easily lead to misdiagnosis, which frequently brings about ankle medial instability and talus shift that eventually lead to the occurrence of ankle osteoarthritis. This study is aimed to investigate the value of the tap test for assessing the integrity of the deltoid ligament intraoperatively. Ninety-two patients with malleolar fractures and possible acute deltoid ligament injury treated in our hospital from March 2013 to May 2016 were enrolled in this prospective study. The gravity stress test and tap test were performed preoperatively by three physicians independently before and after fixation of the fibula. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of both tests were determined based on medial malleolus exploration for the integrity of the deltoid ligament. The inter-observer consistency was also analyzed. Forty seven (51.1%) versus fifty two (56.5%) of the 92 patients tested positive for deltoid ligament injury according to the preoperative gravity stress test or the subsequent tap test. Forty-eight cases (52.2%) were confirmed during surgery. The sensitivity of gravity stress test was lower than that of tap test (95.8% vs 100%), and specificity of gravity stress test was the same as tap test (97.7% vs 97.7%). Between gravity stress test and tap test, the positive and negative predictive values were 97.9% vs 92.3% and 95.6% vs 100%, and the false-positive and false-negative rates were 2.3% vs 9.09% and 4.2% vs 0%, respectively. Between the two tests results, the percentage of inter-observer agreement was > 90% (kappa coefficient > 0.80). The tap test has the advantages of high sensitivity, simple operation, and less radiation exposure, suggesting that it is of high diagnostic value for assessing the integrity of the acute deltoid ligament.

Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite. Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.