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Abstract Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Abstract Purpose Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications. Methods We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed. Results Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation. Conclusion In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety. Chinese clinical trial registry ChiCTR2000033814, Registered 13/ June/2020.

Infected bone defects (IBDs) remains a challenging problem for orthopedists. Clinically, routine management for IBDs has two stages: debridement and systematic antibiotics administration to control infection, and secondary grafting to repair bone defects. Whereas the efficacy is not satisfactory, because the overuse of antibiotics may lead to systemic toxicity, and the emergence of drug-resistant bacteria, as well as the secondary surgery would cause additional trauma and economic burden to the patients. Therefore, it is imperative to develop a novel scaffold for one-stage repair of IBDs. In this study, vancomycin (Van) was encapsulated into poly(lactic co-glycolic acid) (PLGA) microspheres through the double emulsion method, which were then loaded into the additively-manufactured porous tantalum (AM-Ta) through gelatin methacryloyl (GelMA) hydrogel to produce the composite Ta/GelMA hydrogel (Gel)/PLGA/vancomycin(Van) scaffolds for repairing IBDs. Physiochemical characterization of the newly-developed scaffold indicated that the releasing duration of Van was over 2 weeks. Biological experiments indicated good biocompatibility of the composite scaffold, as well as bacteriostasis and osteointegration properties, which showed great potential for clinical application. The construction of this novel scaffold would provide new sight into the development of orthopaedic implants, shedding a novel light on the treatment of IBDs.

Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 1012 events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.

Background Charcot joint disease is a rare neurogenic lesion of the joint characterized by progressive joint destruction with dislocation or subluxation. However, whether a joint replacement should be performed for severe joint damage is controversial. Case presentation This paper reports a case of severe Charcot joint disease with a large bone defect that was treated with arthroplasty assisted by a customized 3D‐printed porous tantalum. The patient was admitted to the hospital with a 9‐year history of bilateral knee pain that had aggravated in the past 2 months. Radiography showed osteogeny and sclerosis in both knees, free bone fragments, heterotopic ossification, new bone, and osteophyte formation, irregular margins, apparent narrowing of joint space, and severe joint damage (Anderson Orthopedic Research Institute classification type III). Based on the present illness, history, imaging, and laboratory examination, Charcot joint disease was confirmed. Conservative treatment has been reported in the literature. There are limited reports on the surgical treatment of severe Charcot joint disease. We followed up with the patient for a year after the operation, and the imaging and clinical evaluation results were good. Postoperative X‐ray examinations showed good alignment of force lines, good joint space, and no evidence of loosening. The patient was mobile and did not need crutches. Conclusions Through accurate surgical evaluation and preparation of 3D‐printed porous tantalum implants, severe AORI classification type III Charcot joint disease can effectively restore the range of motion of the knee joint, the lower limb alignment, and finally achieve good functional results of walking without crutches.

Abstract Background Whether there was clinical superiority for the single‐radius prosthesis over the multi‐radius prothesis in total knee arthroplasty (TKA) still remains to be clarified. We updated a meta‐analysis including prospective randomized controlled trials (RCTs) to compare the clinical prognosis of patients receiving single‐radius TKA (SR‐TKA) or multi‐radius TKA (MR‐TKA). Methods We searched the databases of PubMed, Web of Science, EMBASE, Cochrane Library, MEDLINE for eligible RCTs. Two reviewers evaluated the study quality according to the Risk of Bias tool of the Cochrane Library and extracted the data in studies individually. The extracted data included the baseline data and clinical outcome. The baseline data include the author's name, country, and year of included studies, the name of knee prosthesis used in studies, sample size, follow‐up time, and BMI of patients. The clinical data comprised primary indicators including postoperative knee range of motion (ROM), sit‐to‐stand rest, severe postoperative scorings, such as visual analog scale (VAS), American Knee Society knee score (AKS), Oxford knee scoring (OKS), and SF‐36 Quality of Life Scale, as well as various secondary indicators of complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. The data analysis was performed using Review Manager 5.3 software and STATA 12.0. The sensitivity analysis was performed using STATA 12.0. Results A total of 13 RCTs, along with 1720 patients and 1726 knees, were finally included in our present meta‐analysis. We found that patients in SR‐TKA group performed better in the sit‐to‐stand test (OR = 1.89, 95% CI: 1.05–3.41, p = 0.03) and satisfaction evaluation (OR = 3.27, 95% CI: 1.42–7.53, p = 0.005), which were only evaluated in two included RCTs. While no significant difference was found between SR‐TKA and MR‐TKA groups in terms of postoperative ROM, VAS scoring, AKS scoring, SF‐36 scoring, OKS scoring, and various complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. Conclusion In conclusion, our present meta‐analysis indicated that SR implants were noninferior to MR implants in TKA, and SR implants could be an alternative choice over MR implants, since patients after SR‐TKA felt more satisfied and performed better in the sit‐to‐stand test, with no significant difference in complications between SR‐TKA and MR‐TKA groups. While more relevant clinical trials with long‐term follow‐up time and specific tests evaluating the function of knee extension mechanism should be carried out to further investigate the clinical performance of SR implants.

Abstract Osteosarcoma is the most common malignant tumor in children and adolescents and its diagnosis and treatment still need to be improved. Necroptosis has been associated with many malignancies, but its significance in diagnosing and treating osteosarcoma remains unclear. The objective is to establish a predictive model of necroptosis-related genes (NRGs) in osteosarcoma for evaluating the tumor microenvironment and new targets for immunotherapy. In this study, we download the osteosarcoma data from the TARGET and GEO websites and the average muscle tissue data from GTEx. NRGs were screened by Cox regression analysis. We constructed a prediction model through nonnegative matrix factorization (NMF) clustering and the least absolute shrinkage and selection operator (LASSO) algorithm and verified it with a validation cohort. Kaplan–Meier survival time, ROC curve, tumor invasion microenvironment and CIBERSORT were assessed. In addition, we establish nomograms for clinical indicators and verify them by calibration evaluation. The underlying mechanism was explored through the functional enrichment analysis. Eight NRGs were screened for predictive model modeling. NRGs prediction model through NMF clustering and LASSO algorithm was established. The survival, ROC and tumor microenvironment scores showed significant statistical differences among subgroups (P

Despite the widespread application of Ti6Al4V and tantalum (Ta) in orthopedics, bioinertia and high cost limit their further applicability, respectively, and tremendous efforts have been made on the Ti6Al4V-Ta alloy and Ta coating to address these drawbacks. However, the scaffolds obtained are unsatisfactory. In this study, novel high-interface-strength Ti6Al4V-based porous Ta scaffolds were successfully manufactured using Laser Powder Bed Fusion for the first time, in which porous Ta was directly manufactured on a solid Ti6Al4V substrate. Mechanical testing revealed that the novel scaffolds were biomechanically compatible, and the interfacial bonding strength was as high as 447.5 MPa. In vitro biocompatibility assay, using rat bone marrow mesenchymal stem cells (r-BMSCs), indicated that the novel scaffolds were biocompatible. Alkaline phosphatase and mineralized nodule determination demonstrated that the scaffolds favored the osteogenic differentiation of r-BMSCs. Moreover, scaffolds were implanted into rabbits with femur bone defects, and imaging and histological evaluation identified considerable new bone formation and bone ingrowth, suggesting that the scaffolds were well integrated with the host bone. Overall, these results demonstrated good mechanical compatibility, biocompatibility, and osteointegration performance of the novel Ti6Al4V-based porous Ta scaffold, which possesses great potential for orthopedic clinical applications.

The inflammatory microenvironment created by macrophages has been proven critical for bone regeneration. Both tantalum nanoparticles and micron particles have been applied to bone tissue engineering and have achieved good efficacy, but their effects on immune microenvironment remain unclear. Herein, we explored the different effects between nano- and micro-tantalum particles on the innate immunity of macrophages in vitro and in vivo. RAW 264.7 ​cells were co-cultured with nano- and micro-tantalum particles under inflammatory conditions to evaluate the effects on the morphology and behavior of macrophages. Air pouch model was used to evaluate the material-induced macrophage polarization in vivo. Compared to the tantalum micron particles (TaMPs), the morphology of macrophages was more similar to the M2 phenotype in co-culture with tantalum nanoparticles (TaNPs). At the same time, the TaNPs could also decrease the gene expression of interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), inducible nitric oxide synthase (iNOS), and increase the expression of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10). Furthermore, the air pouch model showed more M2 macrophage infiltration under the intervention of TaNPs. Our findings demonstrated that TaNPs could significantly increase the polarization of M2 macrophages and decrease the macrophage polarization to the M1 phenotype under the inflammatory microenvironment, showing better immunomodulatory properties.

Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (

Segmental bone defects, accompanied by periosteum stripping or injury, usually lead to delayed bone union or nonunion, which have challenged orthopedic surgeons. The periosteum, which provides essential blood supply and initial stem cells for bone tissue, plays an important role in the repair of bone defects. The reconstruction of the destroyed periosteum has attracted the attention of researchers exploring more satisfactory therapies to repair bone defects. However, periosteum-like biomaterials have yet to meet the clinical requirements and resolve this challenging problem. In this study, we manufactured a nanofiber periosteum replacement based on poly-ε-caprolactone (PCL), in which tantalum nanoparticles (TaNPs) and nanoscale magnesium oxide (MgO) were introduced to enhance its osteogenic and angiogenic ability. The results of in vitro experiments indicated that the PCL/Ta/MgO periosteum replacement, with excellent cytocompatibility, promoted the proliferation of both bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs). Furthermore, the incorporation of TaNPs and nano-MgO synergistically enhanced the osteogenic differentiation of BMSCs and the angiogenic properties of EPCs. Similarly, the results of in vivo experiments from subcutaneous implantation and critical-sized calvarial defect models showed that the PCL/Ta/MgO periosteum replacement combined the osteogenesis and angiogenesis abilities, promoting vascularized bone formation to repair critical-sized calvarial defects. The results of our study suggest that the strategy of stimulating repairing bone defects can be achieved with the periosteum repaired in situ and that the proposed periosteum replacement can act as a bioactive medium to accelerate bone healing.

BackgroundsPostoperative wound complication is a major risk factor for the development of Periprosthetic joint infection. We innovatively invented a new dressing system to reduce the occurrence of postoperative wound complications and improve the quality of life of patients after total hip arthroplasty.MethodsA total of 120 patients who underwent primary unilateral total hip arthroplasty were enrolled in this study. The data collected included the number of dressing changes, costs of the dressings, postoperative hospital stay, The Visual Analogue Scale (VAS) score, The Harris Hip Score (HHS), ASEPSIS score, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, the frequency of showers and satisfaction. Data were statistically analyzed.ResultsThe average number of dressing changes was 0.74 ± 0.46, while the average postoperative hospital stay was 3.67 ± 0.97 days. The average cost of the new dressings throughout a treatment cycle was 57.42 ± 15.18 dollars. The VAS score decreased from 5.63 ± 1.09 before the operation to 0.88 ± 0.54 one month after the operation. The HHS score increased from 70.18 ± 7.84 before the operation to 80.36 ± 4.08 one month after the operation. The results of the four indexes of the ASEPSIS score were all 0. The SBSES score was 3.55 ± 0.61 at two weeks after the operation, and 4.38 ± 0.71 at one month after the operation. No wound complications were recorded until one month after the operation when the satisfaction rate was 92.53 ± 3.62%.ConclusionIn this study, we have invented a new dressing system for surgical wounds after total hip arthroplasty and confirmed its efficacy.Chinese Clinical Trial RegistryChiCTR2000033822, Registered 13/ June/2020

PurposeWe devised a novel dressing system to accelerate the recovery after total knee arthroplasty (TKA). The purpose of this study was to assess the clinical outcomes and economic expenses of the new dressing system.MethodsIn this randomized and controlled trial, we enrolled 98 patients who underwent the first unilateral TKA between September 2020 and June 2021. The patients were randomly assigned to one of two groups: the intervention (the new dressing system group) or the control (the traditional gauze dressing) group. We gathered and evaluated patient data including age, gender, body mass index, surgical side, number of dressing changes, post-operative hospital stay, dressing-related expense, satisfaction, pain and function scores, wound scores and wound-related complications.ResultsThe number of dressing changes and post-operative hospital stay in the intervention group were significantly less than in the control group (p = 0.000, p = 0.002). Satisfaction in the intervention group was significantly higher than in the control group's (p = 0.000). There were no significant differences between the two groups in dressing-related expense, pain and function scores. During the one month follow-up, the intervention group's Stony Brook Scar Evaluation Scale (SBSES) was considerably higher than the control group's (p = 0.012).ConclusionThe new dressing system can reduce the number of dressing changes and post-operative hospital stays while increasing patient satisfaction with no difference in medical costs in TKA. This wound dressing system has potential for application in TKAClinical Trial Registrationhttps://clinicaltrials.gov, identifier ChiCTR2000033814.

Osteoarthritis is a chronic degenerative joint disease and its signs of progress mainly attribute to the significant increase of joint friction and the destruction of articular cartilage. Combined cartilage repair and joint lubrication may be a feasible strategy for the treatment of osteoarthritis. In this study, the hydroxypropyl chitin (HPCH)/hyaluronic acid (HA) hydrogel, prepared by physical mixing of HA and HPCH, was designed to be a new bio-lubricant and a chondroprotective agent for osteoarthritis treatment. HA release in HPCH/HA hydrogel was more durable and stable and in vitro experiments showed that HPCH/HA hydrogel could promote the synthesis of the extracellular matrix of chondrocytes. Additionally, HPCH/HA hydrogel could delay the progression of osteoarthritis in DMM-induced osteoarthritis mouse model. To sum up, HPCH/HA hydrogel developed herein can achieve the dual function of well lubrication of joints and protection of cartilage and has the clinical potential as synergetic treatment of osteoarthritis.

BackgroundAugmented reality and mixed reality have been used to help surgeons perform complex surgeries. With the development of technology, mixed reality (MR) technology has been used to improve the success rate of complex hip arthroplasty due to its unique advantages. At present, there are few reports on the application of MR technology in total knee arthroplasty. We presented a case of total knee arthroplasty with the help of mixed reality technology.Case PresentationWe presented a case of a 71-year-old woman who was diagnosed with bilateral knee osteoarthritis with varus deformity, especially on the right side. After admission, the right total knee arthroplasty was performed with the assistance of MR technology. Before the operation, the three-dimensional virtual model of the knee joint of the patient was reconstructed for condition analysis, operation plan formulation, and operation simulation. During the operation, the three-dimensional virtual images of the femur and tibia coincided with the real body of the patient, showing the osteotomy plane designed before the operation, which can accurately guide the completion of osteotomy and prosthesis implantation.ConclusionsAs far as we know, this is the first report on total knee arthroplasty under the guidance of mixed reality technology.

Relevant research shows teachers’ “psychological power” plays a more essential role in promoting their professional development compared with the powers provided by various external factors, and it is therefore held that exploring college English teachers’ individual psychological power is of great significance. To this end, this study investigated college English teachers’ psychological empowerment (CETPE) via the development and validation of CETPE’s scale. Based on our literature review on psychological empowerment and analysis of teachers professional development’s status quo, we made a working definition of CETPE as a system involving perception of their occupation, sense of competence, experiencing of autonomy, judgment of their impact and understanding of their status. In our study, firstly the literature review and the interview with 17 college English teachers were adopted to conceptualize the dimensions of CETPE, and an exploratory factor analysis of data was conducted from 227 college English teachers and then the subsequent confirmatory factor analysis of data collected from another sample of 1030 generated 15 items belonging to five factors. The findings reveal that CETPE is systematically composed of teachers’ positive perception and experience of work meaningfulness, teaching autonomy, occupational competence, professional impact and social status. This study provides a new path for teachers’ professional development via strengthening their intrinsic driving force and thus helps improve the college English teaching effects.

Objective: This study aimed to investigate the impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes. Methods: A total of 118 patients with post-thoracotomy Patient-Controlled Intravenous Analgesia (PCIA) in our hospital from March 2016 to July 2018 were randomly selected and divided into the Composite (COM) Group (57 patients administered with dexmedetomidine [1.0 μg.kg-1 body weight] and morphine [0.48 mg.kg-1 body weight]) and the Morphine (MOR) group (61 patients administered with morphine [0.48 mg.kg-1]). The values of lymphocyte subsets (CD3+, CD4+, and CD8+) and Natural Killer cells in the peripheral blood of these two groups were detected by FACSCalibur flow cytometry at different time points (before anesthesia induction [T0], immediately after tracheal extubation [T1], 12 hours after surgery [T2], 24 hours after surgery [T3], 48 hours after surgery [T4], 72 hours after surgery [T5], and 7 days after surgery [T6]). The doses of morphine at T3 to T5 and the adverse reactions between the two groups were also recorded and compared. Results: The CD3+ level and the CD4+/CD8+ ratio at T2 to T5 and the CD4+ level and NK cells at T3 to T5 were significantly higher in the COM Group than in the MOR Group (p< 0.05). The postoperative morphine dose and the incidence of postoperative itching, nausea, and vomiting were significantly lower in the COM Group than in the MOR Group (p< 0.05). Conclusions: Dexmedetomidine combined with morphine for post-thoracotomy PCIA can improve the function of immunocytes, reduce morphine consumption, and reduce the adverse reactions during analgesia induction. Resumo: Objetivo: Estudar o impacto em linfócitos causado pelo uso da dexmedetomidina associada à morfina para analgesia pós-toracotomia. Método: Um total de 118 pacientes utilizando Analgesia Intravenosa Controlada pelo Paciente (AICP) pós-toracotomia em nosso hospital de Março de 2016 a Julho de 2018 foram selecionados aleatoriamente e divididos em dois grupos: o Grupo Gombinado [COM, 57 pacientes que receberam dexmedetomidina (1,0 μg.kg-1 de peso corpóreo) associada à morfina (0,48 mg.kg-1 de peso corpóreo)] e o Grupo Morfina [MOR, 61 pacientes, que receberam somente morfina (0,48 mg.kg-1)]. Os valores dos subconjuntos de linfócitos (CD3+, CD4+ e CD8+) e das células NK no sangue periférico desses dois grupos foram medidos por citometria de fluxo FACSCalibur em diferentes momentos do estudo [antes da indução anestésica (T0), imediatamente após extubação traqueal (T1), 12 horas após a cirurgia (T2), 24 horas após a cirurgia (T3), 48 horas após a cirurgia (T4), 72 horas após a cirurgia (T5) e 7 dias após a cirurgia (T6)]. As doses de morfina do momento T3 ao T5 e as reações adversas entre os dois grupos também foram registradas e comparadas. Resultados: O nível de CD3+ e a razão CD4+/CD8+ de T2 a T5, e o nível de CD4+ e as células NK de T3 a T5 do Grupo COM foram significantemente maiores (p < 0,05), quando comparados ao Grupo MOR. A dose de morfina no pós-operatório e a incidência de prurido, náusea e vômito no pós-operatório foram significantemente menores no grupo MOR (p < 0,05). Conclusões: Dexmedetomidina combinada com morfina para AICP no período pós-toracotomia pode melhorar a função dos linfócitos, reduzir o consumo de morfina e diminuir reações adversas durante a analgesia.

Introduction: With the development of photothermal technology, the appearance of composite photothermal hydrogels has increased the selectivity of treating infectious skin defects. However, how to design composite photothermal hydrogel with better antibacterial performance, reduce the resistance rate of bacteria, and the damage rate of normal tissue still needs further study.Methods: The Prussian blue and tannic acid were loaded on polyacrylamide hydrogels. Characterization of DLS, Zeta potential, UV absorption spectrum, hydrogel swelling rate, scanning electronic microscopic, drug release profile, photothermal properties, in vitro cytocompatibility, and antibacterial properties. Experiments were measured by skin defect repair, antibacterial detection, and histological staining experiments.Results: The polyacrylamide hydrogel with photothermal effect and controllable release of tannic acid was successfully prepared. The hydrogel has strong light transmittance and adhesion, and the swelling rate can reach 600%, which improves the self-cleaning ability. SEM results showed the porous structure of hydrogels, promoting cell growth. Through photothermal switches, the composite hydrogel represented adjustable and controllable drug release ability. Combined with the synergistic antibacterial effect of tannic acid, this further enhanced the antibacterial ability and reduced the probability of antibiotic resistance. The in vitro and in vivo experiments showed the hydrogel had good biocompatibility and excellent antibacterial properties, which could promote the repair of infectious skin defects in SD rats.Conclusion: We fabricated a hydrogel with a triggering drug release rate, alleviating heat damage, transparent morphology, mechanical stability, strong adhesion, good biocompatibility, and synergistic antibacterial ability, which presents new treatment options for infectious skin defect repair.

Multiple gene-driven programmed cell death 1 ligand 1 (PD-L1)-expressing non-small-cell lung cancer (NSCLC) is very rare. Previous studies have shown that patients with NSCLC with anaplastic lymphoma kinase (ALK) gene rearrangement rarely benefit from PD-L1 inhibitors. Besides the secondary mutations in ALK gene, other mechanisms might contribute to tumor resistance to ALK tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a case of PD-L1-overexpressing lung adenocarcinoma that harbors both EML4-ALK gene rearrangement and BRAF mutation. In particular, a second molecular analysis after resistance to first- and second-generation ALK-TKIs revealed a high PD-L1 expression and tumor mutation burden. Therefore, treatment with nivolumab monotherapy, an anti-PD-1 inhibitor, was started and the patient achieved complete remission. This case report suggested that PD-1 inhibitors might be an effective treatment option for patients with multiple gene-driven PD-L1-expressing NSCLC harboring ALK gene rearrangement.

Abstract Background To investigate the feasibility and clinical efficacy of free vascularized iliac bone flap based on deep iliac circumflex vessels graft for the treatment of osteonecrosis of femoral head (ONFH) in young adults. Methods Eighteen patients (19 hips) undergoing ONFH were included from January 2016 to May 2017. After the debridement of the necrotic bones, the contralateral vascularized iliac bone flap was designed and harvested before grafting, in which the deep circumflex iliac vessels and the transverse branch (or ascending branch) of the lateral circumflex femoral artery and their accompanying veins were anastomosed. X-ray was obtained at 1, 3, 6, 9, and 12 months respectively for evaluation of the bone flap healing. Hip function was evaluated with Harris hip score at 18 months postoperatively. Results None of the patients is lost to follow-up. All the hips healed well except for four complications: one patient developed superficial wound infection, one patient had subcutaneous hematoma, and two patients developed anterolateral femoral cutaneous nerve injury. X-ray films at 12 months showed improvement in 13 hips (68.4%), five hips (26.3%) were unchanged, and one femoral head collapse with conversion to total hip arthroplasty (THA) at 14 months postoperatively (5.3%). Postoperative mean Harris hip scores were significantly improved compared to the preoperative results (P

Abstract Background Minimally invasive endoscopic hematoma evacuation is widely used in the treatment of intracerebral hemorrhage. However, this technique still has room for improvement. The intra-neuroendoscopic technique (INET) is a modified minimally invasive technique, and we report its safety and efficacy in evacuating brain parenchyma hematomas by comparing it with cranial puncture and drainage operation (CPDO). Methods The frontal, temporal, or occipital approaches were used according to the site of bleeding. The preoperative and postoperative hematoma volumes, Glasgow Coma Scale (GCS) score, Cerebral State Index (CSI), hematoma evacuation rate, operation time, complications, and 30-day mortality and Glasgow Outcome Scale (GOS) were retrospectively compared between the two groups. Results A total of 98 patients were enrolled. The evacuation rate (84 ± 7.1% versus 51.0 ± 8.4%, p = 0.00), 7-day GCS (11.8 ± 1.2 versus 10.4 ± 1.5, p = 0.01), and CSI (87.1 ± 8.7 versus 80.6 ± 10.2, p = 0.02) were higher, and the 30-day mortality rate (1.9% versus 15.6%, p = 0.036) was lower in the INET group. However, the operation time was longer in the INET group than in the control group (65.2 ± 12.5 min versus 45.6 ± 10.9 min, p = 0.000). Multivariable logistic regression showed that a good medium-term outcome (GOS scores 4–5) was significantly associated with INET (odds ratio (OR) 3.514, 95% confidence interval (CI) 1.463–8.440, p = 0.005), age under 65 years (OR 1.402, 95% CI, 1.041–1.888, p = 0.026), and hematoma volume less than 50 ml (OR 1.974, 95% CI 1.302–2.993, p = 0.001). Conclusions INET surgery for brain parenchyma hematoma evacuation is a safe and efficient modified technique. This technique is minimally invasive, has less complications, and may be helpful in providing optimal outcomes for selected patients. Trial registration ClinicalTrials.gov, NCT02515903. Registered on 5 August 2015.

Abstract Background In the ultrahigh molecular weight polyethylene (UHMWPE) prosthetic environment, fibroblasts affected by wear particles have the capacity of osteogenesis to reduce osteolysis. We aimed to assess the effects of macrophages on the osteogenic capability of fibroblasts treated with UHMWPE wear particles. Methods The effect of different concentrations of UHMWPE (0, 0.01, 0.1, and 1 mg/ml, respectively) on macrophage proliferation were validated by MTT assay to determine the optimum one. The fibroblasts viability was further determined in the co-culture system of UHMWPE particles and macrophage supernatants. The experiment was designed as seven groups: (A) fibroblasts only; (B) fibroblasts + 1 mg/ml UHMWPE particles; and (C1–C5) fibroblasts + 1/16, 1/8, 1/4, 1/2, and 1/1 supernatants of macrophage cultures stimulated by 1 mg/ml UHMWPE particles vs. fibroblast complete media, respectively. Alizarin red staining was used to detect calcium accumulation. The expression levels of osteogenic proteins were detected by Western blot and ELISA, including alkaline phosphatase (ALP) and osteocalcin (OCN). Results The concentration of 0.1 mg/ml was considered as the optimum concentration for macrophage proliferation due to the survival rate and was highest among the four concentrations. Fibroblast viability was better in the group of fibroblasts + 1/16 ratio of macrophage supernatants stimulated by 1 mg/ml of UHMWPE particles than the other groups (1:8, 1:4, 1:2, 1:1). ALP and OCN expressions were significantly decreased in the group of fibroblasts + 1/4, 1/2, and 1/1 supernatants stimulated by 1 mg/ml of UHMWPE particles compared with other groups (1/8, 1/16) and the group of fibroblasts + 1 mg/ml UHMWPE (p

ObjectivesOsteosarcoma was the most popular primary malignant tumor in children and adolescent, and the 5-year survival of osteosarcoma patients gained no substantial improvement over the past 35 years. This study aims to explore the role of lipid metabolism in the development and diagnosis of osteosarcoma.MethodsClinical information and corresponding RNA data of osteosarcoma patients were downloaded from TRGET and GEO databases. Consensus clustering was performed to identify new molecular subgroups. ESTIMATE, TIMER and ssGSEA analyses were applied to determinate the tumor immune microenvironment (TIME) and immune status of the identified subgroups. Functional analyses including GO, KEGG, GSVA and GSEA analyses were conducted to elucidate the underlying mechanisms. Prognostic risk model was constructed using LASSO algorithm and multivariate Cox regression analysis.ResultsTwo molecular subgroups with significantly different survival were identified. Better prognosis was associated with high immune score, low tumor purity, high abundance of immune infiltrating cells and relatively high immune status. GO and KEGG analyses revealed that the DEGs between the two subgroups were mainly enriched in immune- and bone remodeling-associated pathways. GSVA and GSEA analyses indicated that, lipid catabolism downregulation and lipid hydroxylation upregulation may impede the bone remodeling and development of immune system. Risk model based on lipid metabolism related genes (LMRGs) showed potent potential for survival prediction in osteosarcoma. Nomogram integrating risk model and clinical characteristics could predict the prognosis of osteosarcoma patients accurately.ConclusionExpression of lipid-metabolism genes is correlated with immune microenvironment of osteosarcoma patients and could be applied to predict the prognosis of in osteosarcoma accurately.

Polycarbonate (PCL) has been widely used in tissue engineering, but its hydrophobicity and low biological activity limit its further promotion and application. By adding nanoparticles, the hydrophilicity and biological activity of PCL can be improved. In this study, different amounts of Ta (1–10%wt) were added to PCL, and then their mechanical and biological properties were studied in vitro. XRD found that 5%Ta-PCL has the highest crystallinity. At the same time, cell experiments CCK8, cell adhesion, osteogenic differentiation, and osteogenesis related gene expression showed that Ta can enhance the mechanical and biological properties of PCL, while 5% Ta-PCL showed the best mechanical and biological properties. This composite of tantalum and PCL could have a clinical potential for orthopedic implants.

Objective: The surgical technique, safety, efficacy, and clinical application value of the intra-neuroendoscopic technique (INET) for the treatment of subacute-chronic and chronic septal subdural hematoma was investigated based on the structure and pathological features of the hematoma wall, and the critical factors of hematoma growth and recurrence were determined, in order to provide reference for clinical drug treatment.Methods: This was non-randomized concurrent control study. A total of 94 patients who met the inclusion criteria were recruited between May 2015 and February 2019 and were divided into the INET treatment group (INET group, 45 cases) and the burr hole drainage (BHD) treatment group (control group, 49 cases). The hematoma fluid components and the morphological structure and pathological characteristics of the hematoma wall were analyzed, and the surgical duration, subdural drainage tube (SDT) placement duration, intracranial infection rate, Bender grade at the 1 month post-operative follow-up and hematoma recurrence rate within the 6 months of post-operative follow-up were compared between the two groups. A multiple logistic regression model was established to analyze the risk factors associated with recurrence within 6 months.Results: Intraoperative endoscopy showed that the adhesion bands that formed early in the hematoma cavity were strip-like and that those that formed late were lock-column-like. The hematoma cavity was divided into different-sized chambers with by these strips/columns. Pathological sections of cyst wall reveled angiogenesis inside the cyst and mucus-like changes, rupture and hemorrhage in the vascular wall. Obvious inflammatory cell infiltration and fibrous connective tissue hyperplasia were observed in the cyst wall. The osmotic pressure of the hematoma fluid was not significantly different from that of the peripheral venous blood [(296.7 ± 10.3) mOsm/kg vs. (291.5 ± 12.4) mOsm/kg, p = 0.68]. However, the D-dimer contents which reflect the severity of fibrinolysis in the hematoma and the proinflammatory cytokine interleukin 6 (IL-6) were significantly higher in the hematoma fluid than in the peripheral venous blood. The surgery duration for the INET group was significantly longer than that for the control group [(60.4 ± 10.6) min vs. (44.1 ± 9.8) min, p = 0.00], but both the hematoma recurrence rate within 6 months of post-operative follow-up (4.4 vs. 24.5%, p = 0.00) and the SDT placement duration [(2.1 ± 0.6) d vs. (3.9 ± 0.7) d, p = 0.00] for the INET group were both lower than those for the control group. The intracranial infection rate did not differ significantly between the two groups (4.4 vs. 10.2%, p = 0.50). The overall effective rate of the Bender grade at 1 month of follow-up did not differ significantly between the two groups (95.6 vs. 87.8%, p = 0.32), but the proportion of patients who recovered to Bender grade 0 with no symptoms was significantly higher in the INET group than in the control group (86.7 vs. 67.3%, p = 0.03). Multiple logistic regression analysis showed that INET surgery [odds ratio (OR) 3.71, 95% confidence interval (CI) 1.31–9.62, p = 0.02], age of 65 years or younger (OR 1.51, 95% CI 1.05–2.87, p = 0.03) and unilateral subdural hematoma (OR 1.76, 95% CI 1.05–3.41, p = 0.02) were independent factors that reduced the post-operative recurrence rate.Conclusion: The INET surgical plan based on the structure and pathological features of the subacute-chronic and chronic subdural hematoma wall can reduce the recurrence rate and improve the clinical prognosis.Trial registration:ClinicalTrials.gov, NCT02515903. Registered 5 August, 2015.

Abstract Background The conventional method of core decompression combined with porous bioceramics rod is usually performed under C-arm fluoroscopy for the treatment of early osteonecrosis of the femoral head (ONFH). This study was to evaluate the clinical value and efficacy of three-dimensional (3D) printing guide plate in the process of core decompression plus porous bioceramics rod for the treatment of early ONFH. Methods Forty patients were enrolled, including 20 patients undergoing the surgery with 3D printing guide plate in the experiment group and 20 controls with C-arm fluoroscopy. The following parameters such as surgery time, blood loss, fluoroscopy times, and the accuracy of core decompression for necrosis area, function outcome according to Harris Hip Score (HHS), and any possible complications were recorded and compared between the two groups. All the patients were followed up at 6, 12, and 18 months postoperatively. Results The surgery time, fluoroscopy time, and intraoperative blood loss in the experiment group was significantly less (P 0.05). All patients were followed up for 18 months. There was a significant difference between the preoperative and final follow-up HSS scores in both groups (P

Abstract A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.

Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2) deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones.Bones were deproteinized in H2O2 or pepsin for 8 hours. The morphologies were compared by HE staining. The content of protein and collagen I were measured by the Kjeldahl method and HPLC-MS, respectively. The physical properties were evaluated by SEM and mechanical tests. For in vivo study, X-ray, micro-CT and HE staining were employed to monitor the healing processes of radius defects in rabbit models transplanted with different graft materials.Compared with H2O2 deproteinized bones, no distinct morphological and physical changes were observed. However, pepsin deproteinized bones showed a lower protein content, and a higher collagen content were preserved. In vivo studies showed that pepsin deproteinized bones exhibited better osteogenic performance than H2O2 deproteinized bones, moreover, the quantity and quality of the newly formed bones were improved as indicated by micro-CT analysis. From the results of histological examination, the newly formed bones in the pepsin group were mature bones.Pepsin deproteinized xenograft bones show advantages over conventional H2O2 deproteinized bones with respect to osteogenic capacity; this new method may hold potential clinical value in the development of new biomaterials for bone grafting.

Abstract Objective This study aimed to investigate the impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes. Methods A total of 118 patients with post-thoracotomy Patient-Controlled Intravenous Analgesia (PCIA) in our hospital from March 2016 to July 2018 were randomly selected and divided into the Composite (COM) Group (57 patients administered with dexmedetomidine [1.0 µg.kg-1 body weight] and morphine [0.48 mg.kg-1 body weight]) and the Morphine (MOR) group (61 patients administered with morphine [0.48 mg.kg-1]). The values of lymphocyte subsets (CD3+, CD4+, and CD8+) and Natural Killer cells in the peripheral blood of these two groups were detected by FACSCalibur flow cytometry at different time points (before anesthesia induction [T0], immediately after tracheal extubation [T1], 12 hours after surgery [T2], 24 hours after surgery [T3], 48 hours after surgery [T4], 72 hours after surgery [T5], and 7 days after surgery [T6]). The doses of morphine at T3 to T5 and the adverse reactions between the two groups were also recorded and compared. Results The CD3+ level and the CD4+/CD8+ ratio at T2 to T5 and the CD4+ level and NK cells at T3 to T5 were significantly higher in the COM Group than in the MOR Group (p< 0.05). The postoperative morphine dose and the incidence of postoperative itching, nausea, and vomiting were significantly lower in the COM Group than in the MOR Group (p< 0.05). Conclusions Dexmedetomidine combined with morphine for post-thoracotomy PCIA can improve the function of immunocytes, reduce morphine consumption, and reduce the adverse reactions during analgesia induction.