Finger motor representation supports the autonomy in arithmetic: neuroimaging evidence from abacus training.

Researches have reported the close association between fingers and arithmetic. However, it remains unclear whether and how finger training can benefit arithmetic. To address this issue, we used the abacus-based mental calculation (AMC), which combines finger training and mental arithmetic learning, to explore the neural correlates underlying finger-related arithmetic training. A total of 147 Chinese children (75 M/72 F, mean age, 6.89 ± 0.46) were recruited and randomly assigned into AMC and control groups at primary school entry. The AMC group received 5 years of AMC training, and arithmetic abilities and resting-state functional magnetic resonance images data were collected from both groups at year 1/3/5. The connectome-based predictive modeling was used to find the arithmetic-related networks of each group. Compared to controls, the AMC's positively arithmetic-related network was less located in the control module, and the inter-module connections between somatomotor-default and somatomotor-control modules shifted to somatomotor-visual and somatomotor-dorsal attention modules. Furthermore, the positive network of the AMC group exhibited a segregated connectivity pattern, with more intra-module connections than the control group. Overall, our results suggested that finger motor representation with motor module involvement facilitated arithmetic-related network segregation, reflecting increased autonomy of AMC, thus reducing the dependency of arithmetic on higher-order cognitive functions.

Long-term abacus training gains in children are predicted by medial temporal lobe anatomy and circuitry.

Abacus-based mental calculation (AMC) is a widely used educational tool for enhancing math learning, offering an accessible and cost-effective method for classroom implementation. Despite its universal appeal, the neurocognitive mechanisms that drive the efficacy of AMC training remain poorly understood. Notably, although abacus training relies heavily on the rapid recall of number positions and sequences, the role of memory systems in driving long-term AMC learning remains unknown. Here, we sought to address this gap by investigating the role of the medial temporal lobe (MTL) memory system in predicting long-term AMC training gains in second-grade children, who were longitudinally assessed up to fifth grade. Leveraging multimodal neuroimaging data, we tested the hypothesis that MTL systems, known for their involvement in associative memory, are instrumental in facilitating AMC-induced improvements in math skills. We found that gray matter volume in bilateral MTL, along with functional connectivity between the MTL and frontal and ventral temporal-occipital cortices, significantly predicted learning gains. Intriguingly, greater gray matter volume but weaker connectivity of the posterior parietal cortex predicted better learning outcomes, offering a more nuanced view of brain systems at play in AMC training. Our findings not only underscore the critical role of the MTL memory system in AMC training but also illuminate the neurobiological factors contributing to individual differences in cognitive skill acquisition. A video abstract of this article can be viewed at https://youtu.be/StVooNRc7T8. RESEARCH HIGHLIGHTS: We investigated the role of medial temporal lobe (MTL) memory system in driving children's math learning following abacus-based mental calculation (AMC) training. AMC training improved math skills in elementary school children across their second and fifth grade. MTL structural integrity and functional connectivity with prefrontal and ventral temporal-occipital cortices predicted long-term AMC training-related gains.

Enhanced intersubject similarity in functional connectivity by long-term abacus training.

The individual difference of intrinsic functional connectivity is increasingly acknowledged to be biologically informative and behaviorally relevant. However, such valuable information is still discounted as a stochastic variation in previous studies of cognitive training. Here, we explored the plasticity of intersubject similarity in functional connectivity (ISFC), induced by long-term abacus-based mental calculation (AMC) training. Using a longitudinal dataset (AMC: n = 40, 5-year training; Control: n = 43), we found robust training effect of enhanced ISFC, after accounting for the factor of development. Notably, the enhancement focused on selective subsets of FCs, or the "critical FCs," which predominantly impacted the default-mode and visual networks. Using a cross-sectional dataset with a larger sample (AMC: n = 93, 1/3/5-year training; Control: n = 110), we observed that the "critical FCs" and its intersubject similarity could predict mental calculation ability and its intersubject similarity, respectively, in the AMC group. However, such predictions cannot be generalized to the control group, suggesting that long-term training may be a prerequisite for establishing such brain-behavior relationships. Jointly, our findings implicated that the enhanced ISFC with profound impact on the default-mode network could be a plastic change that is associated with behavioral gains of training.

Core decompression with ß-tri-calcium phosphate grafts in combination with platelet-rich plasma for the treatment of avascular necrosis of femoral head.

BACKGROUND: This study was aimed to investigate whether the application of platelet-rich plasma (PRP) combined with ß-tri-calcium phosphate (ß-TCP) grafts after core decompression (CD) could improve the clinical outcomes of early stage of avascular necrosis of femoral head. METHODS: Forty-five (54 hips) patients with Ficat-Arlet classification stage I-II treated by CD with ß-TCP grafts with or without the application of PRP from July 2015 to October 2020 were reviewed. Group A (CD + ß-TCP grafts) included 24 patients (29 hips), while group B (CD + ß-TCP grafts + PRP) included 21 patients (25 hips). Visual analogue scale (VAS) score, Harris hip score (HHS), change in modified Kerboul angle and the hip joint survival were evaluated and compared between the groups. Patients had a mean follow-up period of 62.1 ± 17.2 months and 59.3 ± 14.8 months in group A and group B, respectively. RESULTS: The mean VAS scores in group A was significantly higher than group B at the 6 months (2.9 ± 0.7 vs 1.9 ± 0.6, p < 0.01) and final follow up postoperative (2.8 ± 1.2 vs 2.2 ± 0.7, p = 0.04). The mean HHS in group A was significantly lower than group B at the 6 months (80.5 ± 13.8 vs 89.8 ± 12.8, p = 0.02). However, at the final follow up, there is no significant difference between the groups (77.0 ± 12.4 vs 83.1 ± 9.3, p = 0.07). The mean change in modified Kerboul angle was -7.4 ± 10.6 in group A and -19.9 ± 13.9 in group B which is statistically significant (p < 0.01). Survivorship from total hip arthroplasty were 86.2%/84% (p = 0.86) at the final follow up, which was not statistically significant. No serious complications were found in both groups. CONCLUSIONS: A single dose of PRP combined with CD and ß-TCP grafts provided significant pain relief, better functional outcomes, and delayed progression in the short term compared to CD combined with ß-TCP grafts. However, the prognosis of the femoral head did not improve significantly in the long term. In the future, designing new implants to achieve multiple PRP injections may improve the hip preservation rate.

Adaptive Reconfiguration of Intrinsic Community Structure in Children with 5-Year Abacus Training.

Human learning can be understood as a network phenomenon, underpinned by the adaptive reconfiguration of modular organization. However, the plasticity of community structure (CS) in resting-state network induced by cognitive intervention has never been investigated. Here, we explored the individual difference of intrinsic CS between children with 5-year abacus-based mental calculation (AMC) training (35 subjects) and their peers without prior experience in AMC (31 subjects). Using permutation-based analysis between subjects in the two groups, we found the significant alteration of intrinsic CS, with training-attenuated individual difference. The alteration of CS focused on selective subsets of cortical regions ("core areas"), predominantly affiliated to the visual, somatomotor, and default-mode subsystems. These subsystems exhibited training-promoted cohesion with attenuated interaction between them, from the perspective of individuals' CS. Moreover, the cohesion of visual network could predict training-improved math ability in the AMC group, but not in the control group. Finally, the whole network displayed enhanced segregation in the AMC group, including higher modularity index, more provincial hubs, lower participation coefficient, and fewer between-module links, largely due to the segregation of "core areas." Collectively, our findings suggested that the intrinsic CS could get reconfigured toward more localized processing and segregated architecture after long-term cognitive training.

Mortality reduction in pediatric patients with severe fatal human adenoviral pneumonia treated with high titer neutralizing antibodies (NAbs) plasma: a retrospective cohort study.

BACKGROUND: Severe fatal human adenoviral (HAdV) pneumonia is associated with significant mortality and no effective drug is available for clinical therapy. We evaluated the association and safety of high titer neutralizing antibodies (NAbs) plasma in pediatric patients with severe fatal HAdV pneumonia. METHODS: A retrospective cohort study was performed between January 2016 to June 2021 in pediatric intensive care unit. Pediatric patients with severe fatal HAdV pneumonia were included and divided into plasma group (conventional treatment plus high titer NAbs plasma treatment) and control group (conventional treatment alone). The primary outcome was mortality in hospital. Secondary outcomes were the duration of fever after adenovirus genotype determined, duration of invasive mechanical ventilation, length of hospital stay. T-test, Mann-Whitney U-test, chi-square test, univariable and multivariable logistic regression analysis, Kaplan-Meier method and log-rank test were adopted to compare differences between two groups. RESULTS: A total of 59 pediatric patients with severe fatal HAdV pneumonia were enrolled. They were divided into plasma group (n = 33) and control group (n = 26). The mortality in hospital was 28.8% (17/ 59). Significantly fewer patients progressed to death in plasma group than control group (18.2% vs 42.3%, p = 0.042). Sequential organ failure assessment (SOFA) score, oxygen index (OI) and high titer NAbs plasma treatment were included in multivariable logistic regression analysis for mortality risk factors. Consequentially, SOFA score (Hazard Ratio [HR] 7.686, 95% Confidence Interval [CI] 1.735-34.054, p = 0.007) and without high titer NAbs plasma treatment (HR 4.298, 95%CI 1.030-17.934, p = 0.045) were significantly associated with mortality. In addition, high titer NAbs plasma treatment were associated with faster temperature recovering in survivors (p = 0.031). No serious adverse effects occurred. CONCLUSIONS: Administration of high titer NAbs plasma were associated with a lower hazard for mortality in pediatric patients with severe fatal HAdV pneumonia. For survivors, high titer NAbs plasma treatment shorten the duration of fever.

ULMR: An Unsupervised Learning Framework for Mismatch Removal.

Due to radiometric and geometric distortions between images, mismatches are inevitable. Thus, a mismatch removal process is required for improving matching accuracy. Although deep learning methods have been proved to outperform handcraft methods in specific scenarios, including image identification and point cloud classification, most learning methods are supervised and are susceptible to incorrect labeling, and labeling data is a time-consuming task. This paper takes advantage of deep reinforcement leaning (DRL) and proposes a framework named unsupervised learning for mismatch removal (ULMR). Resorting to DRL, ULMR firstly scores each state-action pair guided by the output of classification network; then, it calculates the policy gradient of the expected reward; finally, through maximizing the expected reward of state-action pairings, the optimal network can be obtained. Compared to supervised learning methods (e.g., NM-Net and LFGC), unsupervised learning methods (e.g., ULCM), and handcraft methods (e.g., RANSAC, GMS), ULMR can obtain higher precision, more remaining correct matches, and fewer remaining false matches in testing experiments. Moreover, ULMR shows greater stability, better accuracy, and higher quality in application experiments, demonstrating reduced sampling times and higher compatibility with other classification networks in ablation experiments, indicating its great potential for further use.

[Discovery and confirmation of protein action site AK1 of ginsenosides in brain based on DARTS technology].

This study aims to explore the targets of ginsenosides in brain based on drug affinity responsive target stability(DARTS) technology. Specifically, DARTS technology was combined with label-free liquid chromatography tandem mass spectrometry(LC-MS) to screen out the proteins in the brain that might interact with ginsenosides. Based on the screening results, adenylate kinase 1(AK1) was selected for further confirmation. First, the His-AK1 fusion protein was yielded successively through the construction of recombinant prokaryotic expression vector, expression of target protein, and purification of the fusion protein. Biolayer interferometry(BLI) was employed to detect the direct interaction of Rg_1, Re, Rb_1, Rd, Rh_2, F1, Rh_1, compound K(CK), 25-OH-PPD, protopanaxa-diol(PPD), and protopanaxatriol(PPT) with AK1, thereby screening the ginsenoside monomer or sapogenin that had strong direct interaction with the suspected target protein AK1. Then, the BLI was used to further determine the kinetic parameters for the binding of PPD(strongest interaction with AK1) to His-AK1 fusion protein. Finally, molecular docking technology was applied to analyze the binding properties between the two. With DARTS and LC-MS, multiple differential proteins were screened out, and AK1 was selected based on previous research for target verification. Fusion protein His-AK1 was obtained by prokaryotic expression, and the response(nm) of Re, Rg_1, Rd, Rb_1, Rh_1, Rh_2, F1, PPT, PPD, 25-OH-PPD, and CK with His-AK1 was respectively 0.003 1, 0.001 9, 0.042 8, 0.022 2, 0.013 4, 0.037 3, 0.013 9, 0.030 7, 0.140 2, 0.016 0, and 0.040 8. The K_(on), K_(off), and K_D values of PPD and His-AK1 were determined by the BLI as 1.22×10~2 mol~(-1)·L·s~(-1), 1.04×10~(-2) s~(-1), 8.52×10~(-5) mol·L~(-1). According to the molecular docking result, PPD bound to AK1 with the absolute value of the docking score of 3.438, and hydrogen bonds mainly formed between the two. Thus, AK1 is one of the protein action sites of ginsenosides in the brain. The direct interaction between ginsenoside metabolite PPD and AK1 is the strongest.

Adherence with lipid screening guidelines in standard- and high-risk children and adolescents.

Because atherosclerosis begins in childhood, universal lipid screening is recommended with special attention to conditions predisposing to early atherosclerosis. Data about real-world penetration of these guidelines is not available. METHODS: Retrospective cohort study using MarketScan® commercial and Medicaid insurance claims databases, a geographically representative sample of U.S. children. Subjects who passed through the 9- to 11-year window and had continuous insurance coverage between 1/1/2013 and 12/31/2016 were studied. Multivariable models were calculated, evaluating the association between other patient factors and the likelihood of screening. The primary hypothesis was that screening rates would be low, but that high-risk conditions would be associated with a higher likelihood of screening. RESULTS: In total, 572,522 children (51% male, 33% black, 11% Hispanic, 51% Medicaid) were studied. The prevalence of high-risk conditions was 2.2%. In unadjusted and adjusted analyses, these subjects were more likely to be screened than standard-risk subjects (47% vs. 20%, OR: 3.7, 95% CI 3.5-3.8, P < .001). Within this group, the diagnosis-specific likelihood of screening varied (26-69%). Endocrinopathies (OR 5.4, 95% CI 5.2-5.7), solid organ transplants (OR 5.0, 95% CI 3.8-6.6), and metabolic disease (OR 3.9, 95% CI 3.1-5.0, all P < .001) were associated with the highest likelihood of undergoing screening. CONCLUSIONS: Despite national recommendations, lipid screening was performed in a minority of children. Though subjects with high-risk conditions had a higher likelihood of screening, rates remained low. This study highlights the need for research and advocacy regarding obstacles to lipid screening of children in the United States.

Growth in Children with a Fontan Circulation.

OBJECTIVE: To evaluate growth in a population of patients with Fontan circulation. STUDY DESIGN: We performed a cross-sectional evaluation of patients followed in our multidisciplinary Fontan clinic from January 2011 through August 2015. We reviewed the historical data, anthropometry, clinical, and laboratory studies and performed bivariate and multivariate analysis of factors associated with height z score. RESULTS: Patients (n = 210) were included in the study at median age 11.07 years (8.3, 14.73 years) (43% female); 138 (65%) had a dominant right systemic ventricle and 92 (44%) hypoplastic left heart syndrome. Median age at completion of Fontan circulation was 31 months (7.6, 135.8 months). Median height z score was -0.58 (-1.75, 0.26). Twenty-five (12%) had current or past history of protein-losing enteropathy (PLE). Median height z score for those with current or past history of PLE was -2.1 (-2.46, 1.24). Multivariate analysis revealed positive associations between height z score and body mass index z score, time since Fontan, mid-parental height, dominant systemic ventricle type, and serum alkaline phosphatase. Height correlated negatively with known genetic syndrome, PLE, use of stimulant or oral steroid medication. CONCLUSIONS: Children with Fontan circulation have mild deficits in height, with greater deficits in those with PLE. Height z score improves with time postsurgery. Improving weight, leading to improved body mass index, may be a modifiable factor that improves growth in those who are underweight. Biochemical markers may be helpful screening tests for high-risk groups in whom to intensify interventions.

Kaempferol potentiates the sensitivity of pancreatic cancer cells to erlotinib via inhibition of the PI3K/AKT signaling pathway and epidermal growth factor receptor.

Erlotinib (ERL) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) of pancreatic cancer (PC). However, the clinical efficacy of ERL is limited due to the activation of alternative pathways that bypass the EGFR signaling. Kaempferol (KAE), a natural flavonoid compound, has been reported to possess potent anti-tumor and anti-inflammatory properties, and in this study, we aimed at identifying the sensitization effect of KAE on ERL monotherapy in PC cells and mouse models. Briefly, the CCK-8, colony formation, and flow cytometry were used to assess the proliferation and apoptosis of two PC cell lines in response to a treatment combination of KAE and ERL. Additionally, the drug-disease targets and related anti-PC mechanisms of KAE and ERL were predicted with a network pharmacology method. The survival outcome for PC patients with EGFR differential expression was evaluated through survival analysis. The molecular docking technique predicted the affinity between KAE and EGFR. Moreover, western blot (WB) and immunohistochemistry (IHC) analyses were applied to verify the expression levels of related proteins. As a result, in vitro results showed that the combination of KAE and ERL significantly inhibited cell proliferation and promoted cell apoptosis compared to that with ERL alone. Network pharmacology results demonstrated that KAE sensitized PC to ERL treatment may likely be related to the PI3K/AKT signaling pathway and EGFR TKI resistance. Survival analysis illustrated that PC patients with high expression of EGFR had a relative lower survival rate. Molecular docking results further suggested that KAE had a high binding affinity of - 8.9 kcal/mol with EGFR. WB results indicated that the combination of KAE and ERL dramatically downregulated the expression levels of p-EGFR, p-AKT, p-ERK1/2, and Bcl-2, and upregulated the expression levels of cleaved caspase-9, cleaved PARP, and Bax. The in vivo results revealed that treatment combination of KAE and ERL further reduced the volume and weight of subcutaneous grafted tumors. IHC results confirmed the WB results. These data imply that KAE may be a valid therapeutic candidate to potentiate PC cell sensitivity to ERL via inhibiting PI3K/AKT and EGFR signaling.

Training on Abacus-Based Mental Calculation Enhances Visuospatial Working Memory in Children.

Abacus-based mental calculation (AMC) involves temporary storage and manipulation of an imaginary abacus closely related to the function of visuospatial working memory (VSWM). The present study thus investigated the effects of AMC training on VSWM and its neural correlates. A total of 144 human subjects (67 boys) were assigned to AMC or control groups at their entry to primary school. The AMC group received 2 h AMC training per week for 5 school years, whereas the control group spent the time in activities, such as conventional calculation and reading. Raven's Intelligence Test was administered both before and after training. Two arithmetic tests and a VSWM task were conducted after training. Among these participants, fMRI data were collected from 64 children for the VSWM task. Behavioral results indicated that the AMC group outperformed controls on both arithmetic and VSWM tasks, but not on Raven's Intelligence Test. While the two groups activated similar regions during the VSWM task, the AMC group showed greater activation than the controls in frontal, parietal, and occipital areas. Interestingly, the activation of right middle frontal gyrus mediated the relation between the arithmetic ability and the VSWM performance in the AMC group, suggesting that the frontal region may be the neural substrate underlying the transfer effect from AMC training to VSWM. Although the transfer effects seem quite limited considering the length and intensity of the training, these findings suggest that long-term AMC training not only improves arithmetic ability but also has a potential positive effect on VSWM.SIGNIFICANCE STATEMENT Plasticity of working memory is one of the most rapidly expanding research fields in the developmental and cognitive sciences. Previous studies suggest that abacus-based mental calculation (AMC) relies on a visuospatial imaginary strategy, which is closely related to visuospatial working memory (VSWM). However, the impacts of AMC training on VSWM and the underlying neural basis remain unclear. Here, we found that AMC training enhanced VSWM in children, which was accompanied by altered activation in frontal, parietal, and occipital areas. Moreover, we observed that activation in right middle frontal gyrus played a significant mediation role in the transfer of AMC training to VSWM. These findings provide a new perspective to VSWM training and also advance our understanding of related brain plasticity.

Modular segregation of task-dependent brain networks contributes to the development of executive function in children.

Executive function (EF) refers as to a set of high-level cognitive abilities that are critical to many aspects of daily life. Despite its importance in human daily life, the neural networks responsible for the development of EF in childhood are not well understood. The present study thus aimed to examine the development of task-dependent brain network organization and its relationship to age-related improvements in EF. To address this issue, we recruited eighty-eight Chinese children ranging in age from 7 to 12 years old, and collected their functional magnetic resonance imaging (fMRI) data when they performed an EF task. By utilizing graph theory, we found that the task-dependent brain network modules became increasingly segregated with age. Specifically, the intra-module connections within the default-mode network (DMN), frontal-parietal network (FPN) and sensorimotor network (SMN) increased significantly with age. In contrast, the inter-module connections of the visual network to both the FPN/SMN decreased significantly with age. Most importantly, modular segregation of the FPN significantly mediated the relationship between age and EF performance. These findings add to our growing understanding of how development changes in task-dependent brain network organization support vast behavioral improvements in EF observed during childhood.

Structure-activity relationship analysis of dammarane-type natural products as muscle-type creatine kinase activators.

Muscle-type creatine kinase (CK-MM) is the target protein of ginsenosides in skeletal muscle. 20(S)-protopanaxadiol [20(S)-PPD] is an activator of CK-MM and exerts an anti-fatigue effect. In this study, twelve dammarane-type compounds were used for structure-activity relationship analysis in terms of enzyme activity, intermolecular interaction, and molecular docking. Enzyme activity analysis showed that 20(S)-PPD, 20(R)-PPD, 20(S)-protopanaxatriol [20(S)-PPT], 25-OH-PPD, 24-COOH-PPD, panaxadiol (PD), and ginsenoside Rh2 significantly increased CK-MM activity. Panaxatriol (PT), ocotillol, ginsenoside Rg1, and ginsenoside Rd had no significant influence on CK-MM activity, while jujubogenin inhibited its activity. Biolayer Interferometry (BLI) assay produced the same results as those on enzyme activity. The interaction intensity between dammarane-type compounds and CK-MM was linearly related to the compounds' maximum increment rate of enzyme activity. Molecular docking showed the following sequence of docking scores: Rd > Rg1 > Rh2 > 24-COOH-PPD > 20(S)-PPD > 20(S)-PPT > 25-OH-PPD > 20(R)-PPD > ocotillol > PT > PD > jujubogenin. We demonstrated that 20(S)-PPD was the best activator of CK-MM among the 12 dammarane-type compounds. The cyclization of the dammarane side chain, the hydroxyl group at position C6, and the glycosylation of C3, C6, and C20 reduced the ability to activate CK-MM. These findings can help in the development of enhanced CK-MM activators through structural modification.

Auditory and language contributions to neural encoding of speech features in noisy environments.

Recognizing speech in noisy environments is a challenging task that involves both auditory and language mechanisms. Previous studies have demonstrated human auditory cortex can reliably track the temporal envelope of speech in noisy environments, which provides a plausible neural basis for noise-robust speech recognition. The current study aimed at teasing apart auditory and language contributions to noise-robust envelope tracking by comparing the neural responses of 2 groups of listeners, i.e., native listeners and foreign listeners who did not understand the testing language. In the experiment, speech signals were mixed with spectrally matched stationary noise at 4 intensity levels and listeners' neural responses were recorded using electroencephalography (EEG). When the noise intensity increased, the neural response gain increased in both groups of listeners, demonstrating auditory gain control. Language comprehension generally reduced the response gain and envelope-tracking precision, and modulated the spatial and temporal profile of envelope-tracking activity. Based on the spatio-temporal dynamics of envelope-tracking activity, a linear classifier can jointly decode the 2 listener groups and 4 levels of noise intensity. Altogether, the results showed that without feedback from language processing, auditory mechanisms such as gain control can lead to a noise-robust speech representation. High-level language processing modulated the spatio-temporal profile of the neural representation of speech envelope, instead of generally enhancing the envelope representation.

The prognostic significance of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in giant cell tumor of the extremities.

BACKGROUND: In this study, the influence of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of giant cell tumor (GCT) of the extremities were investigated. METHODS: The clinical parameters of 163 patients who were diagnosed with GCT of the extremities between July 2008 and January 2018 were retrospectively analyzed. Optimal cutoff values of NLR and PLR were determined using receiver operating characteristic (ROC) analysis. According to optimal cutoff values, patients were divided into high NLR and low NLR groups or high PLR and low PLR groups. Kaplan-Meier and log-rank methods were used to compare the recurrence-free survival (RFS) between the high and low NLR groups, and between the high and low PLR groups. Univariate analysis was performed to determine the influence of age, gender, neutrophil count, lymphocyte count, platelet count, white blood cell count, tumor size, surgical approach and Campanacci stage on the prognosis of giant cell tumor of bone. The main predictors of RFS were determined by Cox multivariate regression analysis. RESULTS: The optimal cutoff value of NLR in giant cell tumor of the extremities was 2.32, which was used to classify patients into high and low NLR groups. The optimal cutoff value of PLR was 116.81, and was used to classify patients into high and low PLR groups. Campanacci stage, tumor maximum diameter, alkaline phosphatase, and C-reactive protein (CRP) were significantly associated with the high NLR and PLR. Cox multivariate regression analysis revealed that the Campanacci stage (HR = 3.28, 95% CI: 1.24~8.69) and NLR (HR = 4.18, 95% CI: 1.83~9.57) were independent prognostic factors for giant cell tumor of the extremities. CONCLUSION: As a novel inflammatory index, NLR has some predictive power for the prognosis of patients with giant cell tumor of the extremities.

Does Resection of the Primary Tumor Improve Survival in Patients With Metastatic Chondrosarcoma?

BACKGROUND: Although surgical resection or amputation has been the mainstay of localized chondrosarcoma management for many decades, its efficacy in patients with metastatic chondrosarcoma remains unknown, and likewise we do not know whether there are any tumor- or patient-related factors associated with better survival after surgery for metastatic chondrosarcoma. QUESTIONS/PURPOSES: (1) Is resection of the primary tumor associated with improved survival in patients with metastatic chondrosarcoma? (2) Which subgroups of patients with chondrosarcoma benefit more from resection in terms of survival? METHODS: We identified 200 of 222 patients with metastatic chondrosarcoma in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2014 based on the exclusion criteria. Among those patients, 107 (53.5%) underwent primary tumor resection or amputation. Patient information, including demographics (patient age, gender, race, year of diagnosis), tumor characteristics (primary site, histologic subtype, tumor grade, tumor size), and treatment (record of operation and radiation), was collected and included in the study. Kaplan-Meier analyses, log-rank tests, competing risks framework, multivariable Cox regression modeling, and interaction tests were conducted to assess the association of primary tumor resection and survival in the overall cohort and subgroups. RESULTS: Resection of the primary tumor was associated with improved overall survival (hazard ratio [HR], 0.481; 95% confidence interval [CI], 0.340-0.680; p < 0.001) and cancer-specific survival (HR, 0.493; 95% CI, 0.343-0.709; p < 0.001) after controlling for confounding variables. After controlling further for age, histologic subtype, and grade, primary tumor resection was associated with a survival advantage in patients with conventional subtype and Grade II chondrosarcoma (conventional subtype: HR, 0.403; 95% CI, 0.260-0.623 for overall survival and HR, 0.396; 95% CI, 0.250-0.627 for cancer-specific survival). However, primary tumor resection was not associated with increased survival in patients with metastatic chondrosarcoma who had the dedifferentiated subtype and Grade III malignancy. CONCLUSIONS: The present study demonstrates a possible favorable association between primary tumor resection and survival in some patients with metastatic chondrosarcoma at initial diagnosis. Specifically, patients with conventional subtypes and Grade II malignancies who underwent primary tumor resection had better survival compared with those patients who did not have primary tumor resection. Thus, there might be a benefit from primary tumor resection in these patients, but given the limitations of this database, further prospective studies or randomized trials are needed to confirm our findings. In the meantime, this information might be helpful to consider when discussing surgical options with patients who have conventional, Grade 2 metastatic chondrosarcoma at diagnosis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Association of hepatitis B infection with high-risk complications in total joint arthroplasty.

BACKGROUND: An increasing number of patients with hepatitis B virus (HBV) infection are undergoing total joint arthroplasty (TJA) surgery in China. Less attention is provided to the special populations and the purpose of this study is to assess the effect of HBV infection on the prognosis TJAs. METHODS: We retrospectively reviewed patients who underwent elective primary hip and knee arthroplasties in Shanghai Huashan Hospital from 2013 to 2016. Non-hepatitis B cohort was built to match the case cohort to identify whether HBV infection was a risk factor associated with postoperative complications. A total number of 196 patients who underwent primary TJAs were involved in the study, including 49 patients with hepatitis B and 147 non-hepatitis B subjects. RESULTS: Among all the patients with TJAs, 5.5% of patients were infected with HBV for the first time. The incidence rate of complications in patients after arthroplasty with hepatitis B infection was significantly higher than that in patients without hepatitis B (10.2% compared to 4.7%, P < 0.01). Surgical related complications (6.1% compared to 3.4%) and general medical complications (4.1% compared to 1.3%) were higher than those in non-B hepatitis group. Compared with non-B hepatitis group, the overall risk of hepatitis B infection increased by 25% (95% CI, 1.04-1.46; p < 0.01). Similar results were obtained for medical and surgical complications. HBV infection presented a 31% increased risk (95% CI, 1.02-1.62; p < 0.01) for medical complication and an 18% increased risk (95% CI, 1.10-1.26; p < 0.01) for surgical complication. No statistical difference was found between the surgical methods and sex. However, a significant difference of C-reactive protein (CRP) level was found between HBV infection group and the matched non-infected group (P < 0.01). CONCLUSION: This is the first study to investigate the risk of perioperative complications of hepatitis B in Chinese TJAs patients. In consideration of the large population of HBV infection in China, more attention and medical care should be provided to patients with HBV infection who need to undergo TJA operation.

Three-dimensional finite element analysis of silk protein rod implantation after core decompression for osteonecrosis of the femoral head.

BACKGROUND: Several methods are available for the treatment of early-stage osteonecrosis of the femoral head. Core decompression with implantation is a widely-used treatment. However, no single implant is recognized as the most effective way to prevent disease progression. Silk has high strength and resiliency. This study explored the possibility of a strong and resilient silk protein biomaterial as a new alternative implant. METHODS: We investigated the biomechanical properties of the silk protein material by regular compression, torsion, and three-point bending tests. We established three-dimensional finite element models of different degrees of femoral head osteonecrosis following simple core decompression, fibula implantation, porous tantalum rod implantation, and silk protein rod implantation. Finally, we compared the differences in displacement and surface stress under load at the femoral head weight-bearing areas between these models. RESULTS: The elastic modulus and shear modulus of the silk protein material was 0.49GPa and 0.66GPa, respectively. Three-dimensional finite element analyses demonstrated less displacement and surface stress at the femoral head weight-bearing areas following silk protein rod implantation compared to simple core decompression (p < 0.05), regardless of the extent of osteonecrosis. No differences were noted in the surface deformation or surface stress of the femoral head weight-bearing areas following silk protein rod, fibula or tantalum rod implantation (p > 0.05). CONCLUSIONS: When compared with simple core decompression, silk protein rod implantation demonstrated less displacement and surface stress at the femoral head weight-bearing area, but more than fibula or tantalum rod implantation. Similar effects on the surface stress of the femoral head between the silk rod, fibula and tantalum rod implantations, combined with additional modifiable properties support the use of silk protein as a suitable biomaterial in osteonecrosis surgery.

Survival analysis of patients with metastatic osteosarcoma: a Surveillance, Epidemiology, and End Results population-based study.

PURPOSE: The present study is aimed at investigating whether (1) primary tumour surgery confers an improved survival on patients with metastatic osteosarcoma and (2) primary tumour surgery influences survival of patients with metastatic osteosarcoma differently according to primary tumour site. METHODS: We retrospectively identified 517 patients with high-grade, metastatic osteosarcoma in the Surveillance, Epidemiology, and End Results (SEER) database between 1994 and 2013. The effect of primary tumour surgery on survival was assessed using Kaplan-Meier analyses, log-rank tests, and multivariate Cox proportional hazard regression modeling. RESULTS: Of those 517 patients with metastatic osteosarcoma in the cohort, 351 patients (68%) underwent primary surgery, and 166 patients (32%) did not undergo surgery. Primary tumour surgery was associated with increased overall survival (hazard ratio (HR) = 0.457, 95% CI 0.354-0.590, p < 0.001) and cancer-specific survival (HR = 0.422, 95% CI 0.325-0.550, p < 0.001). When we focused on different primary tumour sites, receipt of primary tumour surgery significantly prolonged the survival of patients with extremity osteosarcoma (p < 0.05 for overall and cancer-specific survival). However, for patients with pelvis/spine osteosarcoma, both univariate and multivariate analyses indicated that primary tumour surgery might not be associated with improved survival (p > 0.05 for overall and cancer-specific survival). CONCLUSIONS: Our study is the first population-based analysis to provide evidence of a favourable prognostic impact of primary tumour surgery on metastatic extremity osteosarcoma patients but not metastatic axial (pelvis/spine) osteosarcoma patients. Moreover, we found that surgery type (resection of the primary tumor without amputation vs. amputation) did not influence survival in patients with metastatic osteosarcoma.