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Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Abstract It is still a huge challenge to introduce effective crack‐healing ability into energetic composites with a high oxidizer content. In this article, a poly(urea‐urethane) energetic elastomer was prepared by the polycondensation reaction of glycidyl azido polymer (GAP), isophorone diisocyanate (IPDI), and 2‐aminophenyl disulfide (2‐APD). In the poly(urea‐urethane) elastomer structure, the hybrid dynamic lock, including multilevel H‐bonds and disulfide bonds, not only provides abundant dynamic interactions and promotes chain diffusion, but also enhances physical crosslinking density. Such a unique design fabricated the energetic elastomer with robust tensile strength (0.72 MPa), high stretchability (1631%), and outstanding toughness (8.95 MJ/m3) in the field of energetic polymers. Meanwhile, this energetic elastomer exhibited high self‐healing efficiency (98.4% at 60 °C) and heat release (Q = 1750.46 J/g). Experimental and theoretical results adequately explain the self‐healing mechanism, particularly the role of azido units. The high‐solid content (80 wt%) energetic composites based on the energetic elastomer presented outstanding micro‐defect self‐healing (97.8%) and recycling without loss of mechanical performance. The development of smart energetic composites with excellent self‐healing and recyclable ability provides a meaningful way for a wide range of applications in the field of energetic materials.

Abstract Background It is beneficial for society to discover the risk factors associated with surgery and to carry out some early interventions for patients with these risk factors. Few studies specifically explored the relationship between bone marrow lesions (BMLs) and long-term incident joint surgery. Objective To investigate the association between BML severity observed in knee osteoarthritis (OA) patients’ first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of BMLs for the incident knee surgery. Design Retrospective cohort study. Methods We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine the Max BML grades, BML burden grades and Presence BML grades for the medial, lateral, patellofemoral, and total compartments, respectively. Multi-variable logistic regression models examined the association of the BML grades with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined for BML grades referring to 5-year incident knee surgery. Results Totally, 1011 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 74 knees. Max BML grade 2 and grade 3 of medial, patellofemoral and total compartments were strongly and significantly associated with incident surgery. None of the BML grades from lateral compartment was associated with incident surgery. The PPV was low and NPV was high for BMLs. Conclusions BMLs found in the first MRI examination were associated with 5-year incident joint surgery, except for those allocated in lateral compartments. The high NPVs imply that patients without BMLs have a low risk of requiring surgery within 5 years.

The dispersion of reinforced particles is crucial in improving the mechanical properties of ceramic particles reinforced Al matrix composites. In this work, a novel interfacial projection strategy was proposed to improve the dispersion of TiB2 particles in Al-Si composites through high-throughput first-principles calculations with the experimental verification. Firstly, the Al(111)/TiB2(0001) interface model was constructed. Then, the pre-substitution of Si at 2 at. % concentration was employed to simulate the solutionized Al matrix. Secondly, alloying behaviors of 55 elements (10 substitution sites per element) in the Si-Al(111)/TiB2(0001) interface were studied by high-throughput first-principles calculations in terms of the relative interface formation energy and the relative work of adhesion. With these values, a theoretical alloying map for evaluating the dispersion ability of these alloying elements was plotted. Accordingly, the copper mold experiments were conducted to validate the theoretical alloying map. Based on the electron analysis, the enhanced interface bonds by alloying primarily attributed to electron accumulations around Si atom, indicating that the pre-substitution Si atom was vital for a reliable simulation result. Generally, this interfacial projection strategy provides a precise and potent approach in designing high-performance Al matrix composites, and should be applicable to other reinforced particles.

Aims: To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections. Methods: EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection. Results: When 10 mM or higher EDTA-NS concentrations were used for ten minutes, over 99% of S. aureus biofilm formed on all three types of materials was eradicated in terms of absorbance measured at 595 nm and colony-forming units (CFUs) after culturing. Consistently, SEM and CSLM scanning demonstrated that less adherence of S. aureus could be observed on all three types of materials after 10 mM EDTA-NS irrigation for ten minutes. In the rat model, compared with NS irrigation combined with rifampin (Ti-6Al-4V wire-implanted rats: 60% bacteria survived; HXLPE particle-implanted rats: 63.3% bacteria survived), EDTA-NS irrigation combined with rifampin produced the highest removal rate (Ti-6Al-4V wire-implanted rats: 3.33% bacteria survived; HXLPE particle-implanted rats: 6.67% bacteria survived). In the pig model, compared with NS irrigation combined with rifampin (Ti-6Al-4V plates: 75% bacteria survived; HXLPE bearings: 87.5% bacteria survived), we observed a similar level of biofilm disruption on Ti-6Al-4V plates (25% bacteria survived) and HXLPE bearings (37.5% bacteria survived) after EDTA-NS irrigation combined with rifampin. The in vivo study revealed that the biomass of S. aureus biofilm was significantly reduced when treated with rifampin following irrigation and debridement, as indicated by both the biofilm bacterial burden and crystal violet staining. EDTA-NS irrigation (10 mM/10 min) combined with rifampin effectively removes S. aureus biofilm-associated infections both in vitro and in vivo. Conclusion: EDTA-NS irrigation with or without antibiotics is effective in eradicating S. aureus biofilm-associated infection both ex and in vivo. Cite this article: Bone Joint Res 2024;13(1):40–51.

This study aimed to enhance the mechanical properties of high pressure die casting (HPDC) Al9Si0.6Mn alloys by incorporating in-situ TiB2 particles. The effects of TiB2 addition on the microstructure and mechanical properties of as-HPDC Al9Si0.6Mn alloys were investigated. The results showed that TiB2 addition refined the bimodal grain structure and eutectic Si morphology in the central region of the as-HPDC alloys, which was the primary contributor to the mechanical properties. The thickness of the skin region and band zone increased with increasing TiB2 addition, while the central region exhibited a reduced thickness but remained dominant on the entire cross-section. The optimal TiB2 content was found to be 1 wt%, resulting in the 23.4 % reduction in grain size and 10.7 % enhancement in yield strength. The modified strengthening model based on the microstructure features of the central region accurately predicted the yield strengths of as-HPDC alloys. Finally, the morphological strengthening factors induced by TiB2 particles were analytically illustrated in the HPDC Al9Si0.6Mn–TiB2 alloys.

Background: Chronic ankle instability (CAI) is a common sequela following an acute lateral ankle sprain (LAS). To treat an acute LAS more effectively and efficiently, it is important to identify patients at substantial risk for developing CAI. This study identifies magnetic resonance imaging (MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients. Methods: All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1, 2017 to December 1, 2019 were identified. Data were collected using the Cumberland Ankle Instability Tool at final follow-up. Demographic and other related clinical variables, including age, sex, body mass index, and treatment were also recorded. Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS. Results: A total 131 out of 362 patients with a mean follow-up of 3.0 ± 0.6 years (mean ± SD; 2.0–4.1 years) developed CAI after first-episode LAS. According to multivariable regression, development of CAI after first-episode LAS was associated with 5 prognostic factors: age (odds ratio (OR) = 0.96, 95% confidence interval (95%CI): 0.93–1.00, p = 0.032); body mass index (OR = 1.09, 95%CI: 1.02–1.17, p = 0.009); posterior talofibular ligament injury (OR = 2.17, 95%CI: 1.05–4.48, p = 0.035); large bone marrow lesion of the talus (OR = 2.69, 95%CI: 1.30–5.58, p = 0.008), and Grade 2 effusion of the tibiotalar joint (OR = 2.61, 95%CI: 1.39–4.89, p = 0.003). When patients had at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, or inversion tilt test, they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI. Conclusion: MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, and inversion tilt test. Further prospective and large-scale studies are necessary for validation.

Recent theory suggests that both the orienting response and arousal inhibition play roles in the effect of the concealed information test (CIT). However, the neural signatures associated with these two processes remain unclear. To address this issue, participants were motivated to either conceal or reveal crime-related stimulus during CIT while EEG was recorded. By using a temporal principal component analysis, we found that crime-related stimuli produced a larger early P3 than crime-irrelevant stimuli in both the conceal condition and reveal condition. This result suggests that this early P3 reflects an orienting response. In addition, we found that crime-related stimuli elicited a larger frontal negative slow wave than crime-irrelevant stimuli in the conceal condition but not the reveal condition, which suggests that the frontal negative slow wave reflects the arousal inhibition process. These results provide crucial evidence for understanding the neural basis underlying CIT.

Interface characteristics are of great importance in mechanical performance for multi-phases heat-resistant Al alloys. Herein, Al3Sc precipitates were created at both Al/Al9FeNi interface and Al matrix inside Al–Fe-Ni eutectic alloy by microalloyed Sc. Critically, Al3Sc interface precipitates were found to alleviate local lattice distortion at the Al/Al9FeNi interface to improve interface stability. Therefore, this alloy showed superior creep properties over available reports. The underlying mechanisms were quantitatively elucidated by elevated load transfer effect from interface precipitates and enhanced threshold stress from matrix precipitates. Generally, this work provided a solid understanding to optimize the creep property of eutectic Al alloys by manipulating interface structures.

Electronic devices play an increasingly vital role in modern society, and heat accumulation is a major concern during device development, which causes strong market demand for thermal conductivity materials and components. In this paper, a novel thermal conductive material consisting of polydimethylsiloxane (PDMS) and a binary filler system of h-BN platelets and Al2O3 nanoparticles was successfully fabricated using direct ink writing (DIW) 3D printing technology. The addictive manufacturing process not only endows the DIW-printed composites with various geometries but also promotes the construction of a 3D structural thermal conductive network through the shearing force during the printing process. Moreover, the integrity of the thermal conductive network can be optimized by filling the gaps between the BN platelets with Al2O3 particles. Resultingly, the configuration of the binary fillers is arranged by the shearing force during the DIW process, fabricating the thermal conductive network of oriented fillers. The DIW-printed BN/Al2O3/PDMS with 45 wt% thermal conductive binary filler can reach a thermal conductivity of 0.98 W/(m·K), higher than the 0.62 W/(m·K) of the control sample. In this study, a novel strategy for the thermal conductive performance improvement of composites based on DIW technology is successfully verified, paving a new way for thermal management.

Background: Gallbladder cancer (GBC) is among the most lethal malignancies in the world, with a prognosis that is extremely poor. The results of previous studies suggest that tripartite motif containing 37 (TRIM37) contributes to the progression of numerous types of cancer. Nevertheless, there is little knowledge about the molecular mechanisms and functions of TRIM37 in GBC. Methods: A clinical significance assessment was conducted on TRIM37 following its detection by immunohistochemistry. In vitro and in vivo functional assays were performed to investigate the role of TRIM37 in GBC. Results: In this study, TRIM37 is upregulated in GBC tissues, which is associated with decreased histological differentiation, advanced TNM stage, and shorter overall survival rates. In vitro, TRIM37 knockdown inhibited cell proliferation and promoted apoptosis, and in vivo, TRIM37 knockdown suppressed GBC growth. Contrary to this, cell proliferation is increased in GBC cells when overexpression of TRIM37 is expressed. Mechanistic investigations revealed that TRIM37 promotes GBC progression through activation of the Wnt/β‑catenin signaling pathway via degradation of Axin1. Conclusion: The present study suggests that TRIM37 contributes to the development of GBC and thus provides an important biomarker for predicting GBC prognosis and an effective target for therapeutic intervention.

Abstract Reprogramming lipid metabolism is considered a fundamental step in tumourigenesis that influences ferroptosis. However, molecular mechanisms between lipid metabolism and ferroptosis remain largely unknown. Results from the drug screening of 464 inhibitors (for 164 targets) applied to ferroptosis cells indicated that 4 inhibitors targeted bromodomain-containing protein 4 (BRD4) significantly inhibiting erastin-induced ferroptosis. Functional studies proved that the loss of BRD4 weakened oxidative catabolism in mitochondria, protecting cells from the excessive accumulation of lipid peroxides. Mechanism research revealed that the transcriptional levels of fatty acid metabolism-related genes (HADH, ACSL1 and ACAA2) participating in the β-oxidation of fatty acids (FAO) and polyunsaturated fatty acids (PUFAs) synthesis depended on the activity of super-enhancers (SEs) formed by BRD4 and HMGB2 in their promoter regions. Conclusively, this study demonstrated that BRD4 was indispensable for fatty acid metabolism based on its epigenetic regulatory mechanisms and affecting erastin-induced ferroptosis, providing a new theoretical reference for understanding the relationship between lipid metabolism and ferroptosis deeply.

As the most abundant internal mRNA modification, N6-methyladenosine (m6A) RNA methylation has been found to influence many biological events including bone mesenchymal stem cells (BMSCs) osteogenic differentiation. YTH N6-methyladenosine RNA binding protein C2 （YTHDC2） is an m6A reading protein with the ability to mediate the decay of combined methylated mRNA, however its role in BMSCs osteogenic differentiation remains unknown. In this study, we first found an increase of RUNX family transcription factor 2 （RUNX2） expression and a decrease of YTHDC2 expression during the process of BMSCs osteogenic differentiation. Furthermore, we transfected BMSCs with YTHDC2 interference fragment, resulting in an increased content of RUNX2 mRNA and protein inside BMSCs. Finally, through RNA Immunoprecipitation experiments, we confirmed that YTHDC2 protein can bind to RUNX2 mRNA and accelerate its decomposition. Moreover, the immunofluorescence staining also showed a negative correlation between YTHDC2 and RUNX2. In conclusion, during BMSCs osteogenic differentiation, YTHDC2 protein showed decreased expression, resulting in a higher level of RUNX2 (mRNA and protein) expression inside cells, indicating YTHDC2 as a promising molecular target for the regulation of BMSCs osteogenic differentiation.

Introduction: Data from acute ischemic stroke patients throughout 2021 from one district of an archipelago city of China were collected and analyzed retrospectively to determine the management difference due to time lags from onset of symptoms to the arrival at the stroke center (FMCT) of two regions: main island (MI) and outer islets (OIs). Methods: All patients information from 1 January to 31 December 2021 was retrieved through the electronic medical records system of the only stroke center in MI. After screening and exclusion, each patient's medical record was reviewed by two neurologists separately. Before OI patients were allocated to a group, their residential addresses at onset of the stroke were confirmed by telephone. Comparisons were analyzed between the two regions for gender, age, pre-stroke risk factors and peri-admission management parameters. Results: A total of 326 patients met the inclusion criteria: 300 from the MI group and 26 for the OI group. Intergroup comparisons for gender, age and most of the risk factors showed no significant difference. FMCT were shown to be significantly distinct (p

AimsTo evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope.MethodsBased on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system.ResultsSurgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032).ConclusionAlthough surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope.Cite this article: Bone Joint Res 2022;11(8):518–527.

Background: Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-β1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.

Abstract Aims Intralesional curettage is a commonly used treatment for primary bone tumors. However, local recurrence of tumors after curettage remains a major challenge. Questions (1) Is blood pressure related to local recurrence after intralesional curettage for benign or intermediate bone tumors? (2) What’s the impact of tourniquet usage on the risk of recurrence from high blood pressure? Methods This retrospective study evaluated patients receiving intralesional curettage for primary bone tumors from January 2011 to January 2015. A total of 411 patients with a minimum five-year follow-up were included for analysis. Demographic and disease-related variables were first assessed in univariable analyses for local recurrence risk. When a yielded p-value was 5 cm: OR, 3.58; 95% CI, 1.38–9.33; p = 0.009); anatomical site (proximal femur: OR, 2.49; 95% CI, 1.21–5.15; p = 0.014; proximal humerus: OR, 3.34; 95% CI, 1.61–6.92; p = 0.001); and preoperative mean arterial pressure (> 110 mmHg: OR, 2.61; 95% CI, 1.20–5.67; P = 0.015). In subgroup analyses, after adjusting for age, tumor type, lesion size, and anatomical site, tourniquet use modified the preoperative mean arterial pressure - recurrence relationship: when tourniquet was not used, preoperative mean arterial pressure predicted local recurrence (95–110 mmHg, 4.13, 1.42–12.03, p = 0.009; > 110 mmHg, 28.06, 5.27–149.30, p 0.05). Conclusions A high preoperative blood pressure was related to local recurrence after intralesional curettage for primary bone tumors in our study. Tourniquet usage and controlling blood pressure might be beneficial for reducing local recurrence in patients scheduled to receive intralesional curettage for primary bone tumor treatment. Level of evidence Level IV, hypothesis-generating study.

Aims Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81.

IntroductionSchwannomas are tumors arising from Schwan cells of the neural sheath, which rarely occur in the gastrointestinal tract. The aim of the present study was to analyze the clinicopathological features and treatment outcomes of gastrointestinal schwannomas (GISs).MethodsPatients who were diagnosed with GISs in our hospital from January 2010 to December 2021 were selected. Data about demographic characteristics, clinical symptoms, treatment methods and outcomes, pathological results, and follow-up results were retrospectively collected and analyzed.ResultsA total of 78 patients with 79 GISs were included, the female-to-male ratio was 55:23, and the average age was 52.12 ± 12.26 years. One-third (26/78) of the patients were asymptomatic. A total of 79 GISs were removed, and the average size was 3.63 ± 2.03 cm (range, 0.3–10 cm). As for tumor location, 54 GISs were located in the stomach, 14 in the esophagus, 2 in the duodenum, 6 in the colorectum (4 in the colon and 2 in the rectum), and the other 3 in the small intestine. A total of 23 and 55 patients underwent endoscopic and surgical resections, respectively. Compared with surgical resection, endoscopic resection is associated with a smaller diameter, lower cost, and shorter hospital stay. Pathological results revealed that S100 was positive in all the GISs. No recurrence was noticed during a median follow-up of 45 months (range, 6–148 months).ConclusionGISs are rare gastrointestinal tumors with favorable prognoses, which are most commonly seen in the stomach and diagnosed by pathological findings with immunohistochemical staining. Surgical resection remains the standard method for removing GISs, while endoscopic resection may serve as an alternative method for selected patients with GISs and may be attempted in GISs with a diameter of

Abstract Background The Coronavirus Disease 2019 (COVID-19) pandemic has rapidly spread across the whole world and brought strong psychological impact. This study aimed to evaluate the prevalence of post-traumatic stress disorders (PTSD) in the general people of southwestern China and associated factors 1 month after the outbreak of the COVID-19. Methods This study was started on 4–10 Feb 2020 based on online survey. The present work was carried out in the provinces of southeastern China, including Sichuan Province, Guizhou Province, Yunnan Province, and Chongqing City.1593 respondents aged 18 years and above administered to this study. Data on whether they have experienced confirmed or suspected COVID-19 of themselves/family members/acquaintances were also collected, and based on ‘yes’ answers, the number of affected individuals (via COVID-19) were categorized into four exposure levels i.e., non-affected, less, moderately, or significantly affected. The civilian version of the PTSD checklist and the self-reported information about COVID-19 were used. Results The prevalence of PTSD was approximately 25.2%(n = 401/1593). The chances of developing PTSD were 6.053(OR = 6.053, 95% CI 1.394 to 26.280) or 3.673(OR = 3.673, 95% CI 1.738 to 7.765) times higher among respondents who had been significantly and moderately affected than those who had not been affected, accordingly. Male (OR = 1.484, 95% CI 1.147 to 1.920),younger age individuals (40 ~ 49 age group/

Abstract Gastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.

The cyber range has been widely recognized as an effective way to study the technologies of network attack/defense and the vulnerability of network architecture.The endogenous safety and security test site that receives high attention recently is a type of cyber range for cyber space endogenous safety and security technologies.Based on the new situation of cyberspace with 5G development, a test site management technology for virtual-real network settings was proposed, and a test site management architecture based on the endogenously secured software defined network controller was designed.A design of the endogenously secured network control system was also proposed, which used a middle layer forwarding agent to achieve data isolation and supported multiple heterogeneous open-source controllers.Finally, a test site scenario reconfiguration and resource orchestration method was proposed based on a test site networking scheme.

Aims: In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models. Methods: The cell toxicity of different concentrations of EDTA dissolved in NS (EDTA-NS) was assessed by Cell Counting Kit-8 (CCK-8). Various concentrations of EDTA-NS irrigation solution were compared in three female Sprague-Dawley rat models: 1) a skin defect; 2) a bone exposed; and 3) a wound with an intra-articular implant. All three models were contaminated with Staphylococcus aureus or Escherichia coli. EDTA was dissolved at a concentration of 0 (as control), 0.1, 0.5, 1, 2, 5, 10, 50, and 100 mM in sterile NS. Samples were collected from the wounds and cultured. The bacterial culture-positive rate (colony formation) and infection rate (pus formation) of each treatment group were compared after irrigation and debridement. Results: Cell viability intervened below 10 mM concentrations of EDTA-NS showed no cytotoxicity. Concentrations of 1, 2, and 5 mM EDTA-NS had lower rates of infection and positive cultures for S. aureus and E. coli compared with other concentrations in the skin defect model. For the bone exposed model, 0.5, 1, and 2 mM EDTA-NS had lower rates of infection and positive cultures. For intra-articular implant models 10 and 50 mM, EDTA-NS had the lowest rates of infection and positive cultures. Conclusion: The concentrations of EDTA-NS below 10 mM are safe for irrigation. The optimal concentration of EDTA-NS varies by type of wound after experimental inoculation of three types of wound.

BackgroundPeroral endoscopic myotomy (POEM) has shown promising short-term safety and efficacy in pediatric patients, while long-term outcomes are largely unknown. This study aimed to assess the clinical effects of POEM for pediatric achalasia who had a follow-up of at least 5 years.MethodsPediatric patients from a single center who underwent a POEM between October 2011 and November 2016 were, respectively, collected and analyzed for long-term clinical outcomes. Patients were contacted to evaluate their current symptoms and encouraged repeat endoscopy and manometry. The clinical success, procedure-related parameters, adverse events, gastroesophageal reflux disease after POEM, and quality of life were evaluated.ResultsA total of twenty-four patients who underwent POEM in our center were studied, with a mean age of 14.42 ± 2.65. Two of the 24 patients (8.3%) had previous treatment. The mean of the procedure time was 58.67 ± 19.10 min, 8.3% (2/24) of patients experienced perioperative adverse events. The current symptom scores were obtained from 21 patients at a mean follow-up of 92.57 months, the remainder were lost to follow-up after a mean of 38 months. Eckardt scores were significantly improved from preoperative baseline (preoperative 7.67 ± 1.62 vs. current 0.86 ± 1.28, P < 0.001). Long-term overall success was achieved in 95.8% of patients and none required retreatment for symptoms. 12.5% of patients were suffered from clinical reflux. 76.2% of patients expressed satisfaction with POEM. No severe adverse events were observed during the operation and the 5-years follow-up.ConclusionPOEM resulted in successful symptomatic mitigation in a majority of pediatric patients after 5 years. A multi-center large-scale, prospective study is necessary for a confirmed conclusion.

The automotive industry is experiencing a shift to an intelligent and connected paradigm.(Semi-) Autonomous vehicles use a new generation of information and communication technologies to realize a full range of interactions between vehicles and cloud,vehicles and vehicles,vehicles and roads,and vehicles and pedestrian,etc.When cars started to become connected computers on wheels,network security became a major challenge,and because the scope of cyber threats extended from virtual space to physical space,the harm of cybersecurity had risen to human life.The electronic/electrical structure,in-vehicle network structure,and out-of-vehicle network structure of intelligent vehicles were introduced,the security requirements of vehicle networks were elaborated,several cyber-attacks against connected-automated vehicle (CAV) were pointed out,the available defense measures against these attacks were addressed.The advantages and disadvantages of these measures were summarized.Finally,possible defense measures and directions in the future were discussed to further ensure the security of CAV.

ObjectiveCommon peroneal nerve (CPN) injury that leads to foot drop is difficult to manage and treat. We present a new strategy for management of foot drop after CPN injury. The soleus muscular branch of the tibial nerve is directly transferred to the deep fibular nerve, providing partial restoration of motor function.MethodsWe retrospectively reviewed eight patients treated for CPN injury between 2017 and 2019. The soleus muscular branch of the tibial nerve was transferred to the deep fibular nerve to repair foot drop. Electrophysiology was conducted, and motor function was assessed. Motor function was evaluated by measuring leg muscle strength during ankle dorsiflexion using the British Medical Research Council (BMRC) grading system and electromyography (EMG).ResultsIn 10–15 months postoperatively, EMG revealed newly appearing electrical potentials in the tibialis anterior, extensor hallucis longus, and extensor toe longus muscle (N = 7). Two patients achieved BMRC grade of M4 for ankle dorsiflexion, 2 patients achieved M3, 1 patient achieved M2, and 2 patients achieved M1. Four patients showed good functional recovery after surgery and could walk and participate in activities without ankle-foot orthotics.ConclusionSurgical transfer of the soleus muscular branch of the tibial nerve to the deep fibular nerve after CPN injury provides variable improvements in ankle dorsiflexion strength. Despite variable strength gains, 50% of patients achieved BMRC M3 or greater motor recovery, which enabled them to walk without assistive devices.

Background: For nongeriatric patients with femoral neck fractures (FNFs), preoperative evaluation of fracture three-dimensional inclination is essential to identify fracture stability, select appropriate fixation strategies, and improved clinical prognoses. However, there is lack of evaluation system which takes into account both vertical and oblique inclinations. The purpose of this study was to comprehensively investigate the effect of vertical and oblique inclinations on fracture stability and reoperation risks.Methods: We retrospectively reviewed the medical records of 755 FNFs patients with over 2 years follow-up. The 3-D inclination angle in vertical (α) and oblique plane (β) were measured based on CT images. The optimal threshold for unstable 3-D inclination were identified by seeking the highest Youden Index in predicting reoperation and validated in the biomechanical test. According to the cut-off value proposed in the diagnostic analysis, forty-two bone models were divided into seven groups, and were all fixed with traditional three parallel screws. Interfragmentary motion (IFM) was used for comparison among seven groups. The association between reoperation outcome and 3-D inclination was analysed with a multivariate model.Results and Conclusion: The overall reoperation rate was 13.2%. Unstable 3-D inclination angles with an optimally determined Youden index (0.39) included vertical (α > 70°) and oblique (50° 20°/β < −20°) types. Biomechanical validation showed these fractures had significantly greater (p < 0.05) interfragmentary motion (1.374–2.387 mm vs. 0.330–0.681 mm). The reoperation rate in 3-D unstable group (32.7%) is significantly (p < 0.001) higher than that in 3-D stable group (7.9%). Multivariate analysis demonstrated that 3-D inclination angle was significantly (OR = 4.699, p < 0.001) associated with reoperation. FNFs with α > 70°; 50° 20°/β < −20° are real unstable types with significantly worse interfragmentary stability and higher reoperation risks. Fracture inclination in vertical and oblique planes is closely related to reoperation outcomes and may be a useful complement to the way FNFs are currently evaluated.

The right parietal lobe plays an important role in body image, and disorders of body image emerge after lesions in the parietal lobe or with parietal lobe epilepsy. Body image disorder also often accompanies upper-limb amputation, in which the patient misperceives that their missing limb is still part of their body. Cortical reorganization is known to occur after upper-limb amputation, but it is not clear how widespread and to what degree functional connectivity (FC) is reorganized post-amputation, nor whether such changes might be related to misperceptions of body image. Twenty-four subjects who had a traumatically upper-limb amputees (ULAs) and 24 age-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. Regions of interest (ROIs) in the right superior parietal gyrus (SPG_R) and right inferior parietal lobule (IPL_R) were defined using BrainNet Viewer. We calculated the amplitude of low-frequency fluctuations (ALFF) in ROIs and correlated the ROI mean amplitude of low-frequency fluctuations (mALFF) and mean scores on the phantom limb sensation (PLS) scale and beck depression index (BDI). We also calculated ROIs and whole-brain FC. Compared to the HC group, we observed significantly increased activation (mALFF) in ROIs of the ULA group. Moreover, correlation analyses revealed a significant positive correlation between ROI mALFF and scores on the PLS. There was a significant negative correlation between the SPG_R mALFF and BDI scores. Seed-based, whole-brain FC analysis revealed that FC in the ULA group significantly decreased in many brain regions across the entire brain. The right parietal lobe appears to be involved in some aspect of body awareness and depression in amputation patients. Upper-limb amputation results not only in reorganization in the local brain area formerly representing the missing limb, but also results in more widespread reorganization through FC changes in whole brain.

The highly efficient network resources are provided by multi-access edge computing at the edge of the network,but high security capability is required also due to its distributed position and organization.Based on mimic defense theory,mimic defense structure for distributed multi-access edge computing was proposed.By segmenting data,padding check data and processing data at multiple edge node,dynamic scheduling and decision-making functions according to checksum were implemented.The simulation results show that with the increase of delay cost,the data manipulation and leak rates can be reduced effectively by the proposed structure.The edge node scheduling strategy based on trust and cost is proposed to improve the efficiency and security of the system.

Abstract Background Opioids and acetaminophen are both widely used to relieve pain after non-operative treatment of limb fractures, but evidence for the superiority of opioids versus acetaminophen is lacking. In this study, we aim to determine whether acetaminophen is non-inferior to the acetaminophen/oxycodone combination for pain relief after non-operative fixation of an extremity limb fracture. We hypothesize that acetaminophen is non-inferior to the acetaminophen/oxycodone combination. Methods A double-blind randomized controlled trial will be conducted. Power analysis determined that 1226 participants will be needed (P

There has been renewed interest in using relaying systems as a low-cost solution in next generation wireless broadband networks. In this paper, we take a fresh look at relaying and propose a new retransmission protocol for a two-way wireless network with one base-station, one full-duplex relay and multiple users exchanging messages over fading channels. In this scenario, the relay and each user may hear the message from the base-station and other users. To improve the throughput, we apply network-coded ARQ with reverse-link assistance (NC-RLA) at the relay to exploit the overheard side-information acquired from both the downlink and uplink. We analyze the throughput performance enhancements of NC-RLA and validate our mathematical derivations with Monte Carlo simulation. The simulation results show that significant throughput improvements are obtained with the NC-RLA scheme for low/moderate SNRs. We also prove that full-duplex relay increases the throughput if it is located at the optimal position. Otherwise, it is not beneficial to add a relay, especially with a large number of users using network coding.

Background. Amputation in adults is a serious procedure or traumatic outcome, one that leads to a possible “remapping” of limb representations (somatotopy) in the motor and sensory cortex. The temporal and spatial extent underlying reorganization of somatotopy is unclear. The aim of this study was to better understand how local and global structural plasticity in sensory-motor cortical networks changes temporally and spatially after upper-limb amputation. Methods. We studied 8 healthy nonamputee control subjects and 16 complete upper-limb amputees. Resting-state MRI (rs-fMRI) was used to measure local and large-scale relative differences (compared to controls) in both the amplitude of low-frequency fluctuations (ALFF) and degree of centrality (DC) at 2 months, 6 months, and 12 months after traumatic amputation. Results. In amputees, rs-fMRI scans revealed differences in spatial patterns of ALFF and DC among brain regions over time. Significant relative increases in ALFF and DC were detected not only in the sensory and motor cortex but also in related cortical regions believed to be involved in cognition and motor planning. We observed changes in the magnitude of ALFFs in the pre- and postcentral gyrus and primary sensory cortex, as well as in the anterior cingulate, parahippocampal gyrus, and hippocampus, 2 months after the amputation. The regional distribution of increases/decreases in ALFFs and DC documented at 2-month postamputation was very different from those at 6 and 12-month postamputation. Conclusion. Local and wide-spread changes in ALFFs in the sensorimotor cortex and cognitive-related brain regions after upper-limb amputation may imply dysfunction not only in sensory and motor function but also in areas responsible for sensorimotor integration and motor planning. These results suggest that cortical reorganization after upper extremity deafferentation is temporally and spatially more complicated than previously appreciated, affecting DC in widespread regions.

Telecom operators have been committed to the research of illegal voice call governance approach，which includes analyzing the risk origin，determining the management focus and formulating the prevention strategy.Through the establishment of big data analysis platform based on all kinds of call signaling collection，the call features of all kinds of illegal voice call were researched，the control system of illegal voice call（especially fraud call）was constructed，an all-around control was implemented，and the effect was obvious when the system was applied actually.

Autophagy participates in the progression of many diseases, comprising ischemia/ reperfusion (I/R). It is reported that it is involved in the protective mechanism of ischemic postconditioning (IPostC). According to research, neuronal nitric oxide synthase (nNOS) is also involved in the condition of I/R and IPostC. However, the relationship between nNOS, autophagy and IPostC has not been previously investigated. We hypothesize that IPostC promotes autophagy activity against I/R injury partially through nNOS-mediated pathways. Mouse hearts were subjected to I/R injury through the ligation of the left anterior descending coronary artery. H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, restored nNOS activity, increased the formation of autophagosome and restored the impaired autophagic flux, thus autophagic activity was raised markedly. IPostC increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and suppressed mammalian target of rapamycin (mTOR), but a selective nNOS inhibitor abolished those effects. Similar effects of IPostC were demonstrated in H9c2 cells in vitro. IPostC decreased infarct size and preserved most of the normal structure. The level of reactive oxygen species (ROS) and cell apoptosis were reduced by IPostC with improved cell viability and mitochondrial membrane potential. However, an autophagy inhibitor suppressed the protective effects. These results suggest that IPostC promoted autophagy against I/R injury at least partially via the activation of nNOS/AMPK/mTOR pathway.

The rapid proliferation of complex information systems has been met by an ever-increasing quantity of exploits that can cause irreparable cyber breaches. To mitigate these cyber threats, academia and industry have placed a significant focus on proactively identifying and labeling exploits developed by the international hacker community. However, prevailing approaches for labeling exploits in hacker forums do not leverage metadata from exploit darknet markets or public exploit repositories to enhance labeling performance. In this study, we adopted the computational design science paradigm to develop a novel information technology artifact, the deep transfer learning exploit labeler (DTL-EL). DTL-EL incorporates a pre-initialization design, multi-layer deep transfer learning (DTL), and a self-attention mechanism to automatically label exploits in hacker forums. We rigorously evaluated the proposed DTL-EL against state-of-the-art non-DTL benchmark methods based in classical machine learning and deep learning. Results suggest that the proposed DTL-EL significantly outperforms benchmark methods based on accuracy, precision, recall, and F1-score. Our proposed DTL-EL framework provides important practical implications for key stakeholders such as cybersecurity managers, analysts, and educators. [ABSTRACT FROM AUTHOR]