The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death.

Apoptosis, the first regulated form of cell death discovered in mammalian cells, is executed by caspase-3/7, which are dormant in living cells but become activated by upstream caspase-8 or caspase-9 in responding to extracellular cytokines or intracellular stress signals, respectively. The same cell death-inducing cytokines also cause necroptosis when caspase-8 is inhibited, resulting in the activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates pseudokinase MLKL to trigger its oligomerization and membrane-disrupting activity. Caspase-1/4/5/11, known as inflammatory caspases, instead induce pyroptosis by cleaving gasdermin D, whose caspase-cleaved N terminus forms pores on the plasma membrane. The membrane protein NINJ1 amplifies the extent of membrane rupture initiated by gasdermin D. Additionally, disturbance of peroxidation of polyunsaturated fatty acid tails of membrane phospholipids triggers ferroptosis, an iron-dependent and caspases-independent necrotic death. This review will discuss how these regulated cell death pathways act individually and interconnectively in particular cell types to carry out specific physiological and pathological functions.

Multidimensional stitching method with wavelength tuned interferometry and unconstrained support tooling for large-thin parallel plate.

Limited by measurement methods, measuring the surfaces and thickness of large thin parallel plates has been challenging. In this paper, we propose a multi-dimensional stitching method using thickness alignment (MSuTA), which use the sub-aperture stitching method based on the phenomenon of parallel plate self-interference with wavelength-tuned interferometer (WTI) for measuring the surfaces and thickness of large thin parallel plates. We establish the stitching correction model based on Legendre polynomial to separate the aberrations caused by the elastic deformation of the thin plate in the unconstrained support tooling by analyzing the influence of the stress state of the thin plate with unconstrained three-point support. The stitching experiment has carried out on 6.3 mm thick, 6-inch parallel plates that the stitching residual is better than 0.35 nm RMS. Compared with 12-inch vertical interferometer, the surfaces and thickness deviation are better than 0.8 nm RMS, and the 36 standard Legendre polynomial coefficient deviation are better than 2.5 nm. Moreover, MSuTA can improves the lateral resolution of the measurement by nearly four times, allowing for a display of more comprehensive surface information. The stitching method proposed in this paper will be widely applied in the manufacture and measurement of large thin parallel plates, and provide reference for the elastic deformation analysis of the thin optical elements in the unconstrained support tooling.

Aryne and CO2-based formal [2 + 2 + 2] annulation to access tetrahydroisoquinoline-fused benzoxazinones.

Tetrahydroisoquinoline and its fused polyheterocycles are prevalent structural motifs found in numerous natural products. In this study, we report a highly efficient and convergent synthetic approach for the construction of tetrahydroisoquinoline-fused polyheterocycles through a three-component formal [2 + 2 + 2] annulation process by combining 3,4-dihydroisoquinolines, CO2, and benzynes. Notably, electron-rich 3,4-dihydroisoquinolines and electron-deficient benzynes exhibit greater reactivity in this annulation. Moreover, this method benefits from the convergent synthesis and the utilization of carbon dioxide, providing a valuable strategy for the facile synthesis of tetrahydroisoquinoline-fused polyheterocycles, with potential applications in the discovery and development of novel organic molecules.

Preoperative Anemia and Risk of In-hospital Postoperative Complications in Patients with Hip Fracture.

Purpose: To evaluate the impact of preoperative anemia on postoperative complications after hip fracture surgery. Patients and Methods: We conducted a retrospective study including hip fracture patients at a teaching hospital between 2005 and 2022. We defined preoperative anemia as the last hemoglobin measurement level before surgery < 130 g/L for men and < 120 g/L for women. The primary outcome was a composite of in-hospital major complications, including pneumonia, respiratory failure, gastrointestinal bleeding, urinary tract infection, incision infection, deep venous thrombosis, pulmonary embolism, angina pectoris, arrhythmia, myocardial infarction, heart failure, stroke, and death. Secondary outcomes were cardiovascular events, infection, pneumonia, and death. We used multivariate negative binomial or logistic regression to evaluate the impact of anemia and its severity, categorized as mild (90-130 g/L for men, 90-120 g/L for women) or moderate-to-severe (< 90 g/L for both) anemia on outcomes. Results: Of the 3540 included patients, 1960 had preoperative anemia. 188 anemic patients experienced 324 major complications, while 63 non-anemic patients had 94 major complications. The risk of major complications was 165.3 (95% CI, 149.5-182.4) and 59.5 (95% CI, 48.9-72.3) per 1000 persons in anemic and non-anemic patients, respectively. Anemic patients were more likely to have major complications than non-anemic patients (adjusted incidence rate ratio (aIRR), 1.87; 95% CI, 1.30-2.72), which was consistent in mild (aIRR, 1.77; 95% CI, 1.22-2.59) and moderate-to-severe (aIRR, 2.97; 95% CI, 1.65-5.38) anemia. Preoperative anemia also increased the risk of cardiovascular events (aIRR, 1.96; 95% CI, 1.29-3.01), infection (aIRR, 1.68; 95% CI, 1.01-2.86), pneumonia (adjusted odds ratio (aOR), 1.91; 95% CI, 1.06-3.57), and death (aOR, 3.17; 95% CI, 1.06-11.89). Conclusion: Our findings suggest that even mild preoperative anemia is associated with major postoperative complications in hip fracture patients. This finding highlights considering preoperative anemia as a risk factor in surgical decision-making for high-risk patients.

Natural iron minerals in an electrocatalytic oxidation system and in situ pollutant removal in groundwater: Applications, mechanisms, and challenges.

Natural iron-bearing minerals are widely distributed in the environment and show prominent catalytic performance in pollutant removal. This work provides an overview of groundwater restoration technologies utilizing heterogeneous electro-Fenton (HEF) techniques with the aid of different iron forms as catalysts. In particular, applications of natural iron-bearing minerals in groundwater in the HEF system have been thoroughly summarized from either the view of organic pollutant removal or degradation. Based on the analysis of the catalytic mechanism in the HEF process by pyrite (FeS2), goethite (α-FeOOH), and magnetite (Fe3O4) and the geochemistry analysis of these natural iron-bearing minerals in groundwater, the feasibility and challenges of HEF for organic degradation by using typical iron minerals in groundwater have been discussed, and natural factors affecting the HEF process have been analyzed so that appropriate in situ remedial measures can be applied to contaminated groundwater.

Breast Carcinoma with a Special Histological Pattern of Sebaceous Differentiation and High-Frequency Microsatellite Instability: A Case Report and Review of the Literature.

The World Health Organization in its 2019 Classification of Breast Tumors termed breast sebaceous carcinoma as invasive breast carcinoma of no special type (IBC-NST), with a sebaceous pattern. Approximately 30 cases of IBC-NST with a sebaceous pattern have been reported in the literature, and in all cases the expression of mismatch repair proteins in tumors was normal. Here, we report a case of IBC-NST with a sebaceous pattern and high-frequency microsatellite instability (MSI-H). This case was a sporadic sebaceous pattern of IBC-NST with MSI-H and was unrelated to Muir-Torre syndrome. Its histopathological characteristics were similar to those of MSI-H-associated triple-negative breast carcinoma (TNBC) with a high histological grade but were without tumor-infiltrating lymphocytes (TILs). The tumor did not recur after 20 months of follow-up.

The effects of information platform-based nursing on preventing venous thromboembolism in patients with hip fractures.

PURPOSE: Venous thromboembolism (VTE) is a major health issue among hip fracture patients. This study aimed to develop an information platform based on a mobile application and then evaluate whether information platform-based nursing could improve patient's drug compliance and reduce the incidence of VTE in hip fracture patients. METHODS: This study retrospectively analyzed hip fracture patients who were treated with conventional prevention and intervention methods for VTE (control group) between January 2008 and November 2012, and prospectively analyzed hip fracture patients who were treated with nursing intervention based on the information platform (study group) between January 2016 and September 2017. All the patients included in the both groups were hip fracture patients who had an age over 50 years, treated with surgery, and hospitalized ≥ 48 h. Patients were excluded if they admitted to hospital due to old fractures, had a severe bleeding after 72 h of admission, diagnosed with any type of VTE, or refused to participate in the study. The information platform was divided into medical, nursing, and patient interface. Based on the information platform, medical practitioners and nurses could perform risk assessments, monitoring management and early warnings, preventions and treatments, health educations, follow-up, and other aspects of nursing interventions for patients. This study compared essential characteristics, drug compliance, VTE occurrence, and mean length of hospitalization between the two groups. Besides, a subgroup analysis was performed in the study group according to different drug compliances. SPSS 18.0 software (IBM Corp., NY, and USA) was used for statistical analysis. RESULTS: Altogether 1177 patients were included in the control group, and 491 patients in the study group. Regarding baseline data, patients in the study group had more morbidities than those in the control group (p < 0.05). The difference of drug compliance between the two groups was statistically significant (p < 0.001): 761 (64.7%) of the patients in the control group and only 30 (6.1%) patients in the study group had poor drug compliance. In terms of VTE, 10.7% patients (126/1177) in the control group had VTE, and the rate in the study group was 7.1% (35/491), showing a statistically significant difference (p = 0.02). Moreover, the average length of hospitalization in the study group was also significantly lower than that in the control group (10.4 days vs. 13.7 days, p < 0.001). Subgroup analyses of the study group showed that the incidence of VTE in patients with poor, partial, and good compliances were 56.7% (17/30), 5.8% (10/171), and 2.8% (8/290), respectively, revealing a significantly huge difference (p < 0.001). CONCLUSIONS: Poor drug compliance leads to higher VTE occurrence. The information platform-based nursing can effectively improve the compliance of hip fracture patients and thus considerably reduce the incidence of VTE. The mobile application may be an effective tool to prevent VTE in hip fracture patients.

Control the greenhouse gas emission via mediating the dissimilatory iron reduction: Fulvic acid inhibit secondary mineralization of ferrihydrite.

Reducing methane emission is of great importance to control the global greenhouse effect. Dissimilatory iron reduction (DIR) coupling of organic matter decomposition may suppress methane production via reducing primary electron donors available for methanogenesis. However, during DIR, the amorphous iron oxides (e.g., ferrihydrite) are easy to transform into more stable crystalline iron minerals, which slowdowns the rate of DIR. Humic substance (HS) with redox activity has been extensively reported to facilitate DIR via "electron shuttles" mechanism, yet little known about the effect of HS on mediating the mineralization of iron oxides and the subsequent influences on DIR and methanogenesis. To clarify this, ferrihydrite and fulvic acid (FA) (as the model substance of HS) were supplied to anaerobic methanogenesis systems. Results showed that FA could significantly decrease the formation of crystalline iron oxides, enhance DIR rate by 13.72% and suppress methanogenesis by 25.13% compared to ferrihydrite supplemented only. By X-ray absorption spectra analysis, it was found that FA could complex with ferrihydrite via forming a Fe-C/O structure on the second shell of Fe atom. Quantum chemical calculation further confirmed that FA reduced the adsorption energy between Fe(II) and ferrihydrite. Our study suggested that rational use of HS to mediate mineralization pathway of iron oxides could efficiently improve the availability of iron oxides to drive DIR and control the conversion of organics into CH4 in natural or engineered systems.

Expression and Prognosis Analysis of SUMOylation Regulators in Oral Squamous Cell Carcinoma Based on High-Throughput Sequencing.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) originates from oral mucosal epithelial cells, accounting for more than 90% of oral cancers. The relationship between the expression and prognostic role of SUMOylation regulators in OSCC is rarely studied. MATERIALS AND METHODS: The expression and survival data of OSCC were derived from TCGA and GEO databases. Wilcoxon test was used to determine the differential expression of the SUMOylation regulators. A prognostic model based on SUMOylation regulator-related genes was constructed by Cox regression. Gene set enrichment analysis was applied to predict the potential biological functions that the genes might be involved in. RESULTS: RANBP2 and SENP6 had the highest SNV frequency. Eleven genes including PIAS3, RANBP2, USPL1, SENP6, SENP2, SENP5, SAE1, UBA2, PIAS4, UBE2I, and SENP3 were highly expressed in OSCC. The prognostic model based on nine SUMOylation-regulated genes (TRIM37, UFM1, FUBP1, CCNT1, FXR1, HMG20A, RANBP3, SPATA5, and DDX23) had a strong ability to predict the prognosis of OSCC. CONCLUSION: This study might provide targets for prognostic evaluation and targeted therapy of patients with OSCC.

Construction of a SUMOylation regulator-based prognostic model in low-grade glioma.

Low-grade glioma (LGG) is an intracranial malignant tumour that mainly originates from astrocytes and oligodendrocytes. SUMOylation is one of the post-translational modifications but studies of SUMOylation in LGG is quite limited. Transcriptome data, single nucleotide variant (SNV) data and clinical data of LGG were derived from public databases. The differences between the expression of SUMOylation regulators in LGG and normal brain tissue were analysed. Cox regression was used to construct a prognostic model in the training cohort. Kaplan-Meier survival curves and ROC curves were plotted in the training and the validation cohort to evaluate the effectiveness of the prognostic model. GO and KEGG analyses were applied to preliminarily analyse the biological functions. Compared with normal brain tissue, SENP1 and SENP7 were up-regulated and SENP5 was down-regulated in LGG. SUMOylation regulators may be involved in functions such as mRNA splicing, DNA replication, ATPase activity and spliceosome. One prognostic model was established based on the 4 SUMOylation regulator-related signatures (RFWD3, MPHOSPH9, WRN and NUP155), which had a good predictive ability for overall survival. This study is expected to provide targets for the diagnosis and treatment of low-grade glioma.

SUMOylation Regulator-Related Molecules Can Be Used as Prognostic Biomarkers for Glioblastoma.

INTRODUCTION: SUMOylation is one of the post-translational modifications. The relationship between the expression of SUMOylation regulators and the prognosis of glioblastoma is not quite clear. MATERIALS AND METHODS: The single nucleotide variant data, the transcriptome data, and survival information were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and cBioportal database. Wilcoxon test was used to analyze differentially expressed genes between glioblastoma and normal brain tissues. Gene set enrichment analysis was conducted to find the possible functions. One risk scoring model was built by the least absolute shrinkage and selection operator Cox regression. Kaplain-Meier survival curves and receiver operating characteristic curves were applied to evaluate the effectiveness of the model in predicting the prognosis of glioblastoma. RESULTS: Single-nucleotide variant mutations were found in SENP7, SENP3, SENP5, PIAS3, RANBP2, USPL1, SENP1, PIAS2, SENP2, and PIAS1. Moreover, UBE2I, UBA2, PIAS3, and SENP1 were highly expressed in glioblastoma, whereas PIAS1, RANBP2, SENP5, and SENP2 were downregulated in glioblastoma. Functional enrichment analysis showed that the SUMOylation regulators of glioblastoma might involve cell cycle, DNA replication, and other functions. A prognostic model of glioblastoma was constructed based on SUMOylation regulator-related molecules (ATF7IP, CCNB1IP1, and LBH). Kaplain-Meier survival curves and receiver operating characteristic curves showed that the model had a strong ability to predict the overall survival of glioblastoma. CONCLUSION: This study analyzed the expression of 15 SUMOylation regulators in glioblastoma. The risk assessment model was constructed based on the SUMOylation regulator-related genes, which had a strong predictive ability for the overall survival of patients with glioblastoma. It might provide targets for the study of the relationship between SUMOylation and glioblastoma.

Expression and prognostic characteristics of m5 C regulators in low-grade glioma.

Glioma is the most common intracranial malignant tumour. A clear diagnosis and molecular targeted therapy are of great significance for improving the survival time and quality of life of patients with low-grade glioma. 5-methylcytosine methylation is one of the ways of RNA modification, but there are limited studies on the role of m5 C methylation of low-grade glioma. Single-nucleotide variant, RNA expression matrix and corresponding clinical data of low-grade glioma came from public database. The single-nucleotide variant and expression of m5 C regulators were estimated. A prognostic model based on m5 C regulators was constructed by Cox regression. Potential functions of these molecules were assessed by gene set enrichment analysis. DNMT3A mutation was the most frequent among the m5 C regulators in low-grade glioma. NSUN3, TET2, TRDMT1, ALYREF, DNMT3B, DNMT1, NOP2 and NSUN2 were up-regulated. One prognostic model was constructed which had a strong predictive power for the overall survival of low-grade glioma. We studied the expression and prognostic characteristics of m5 C regulators in low-grade glioma, supplied biomarkers for the diagnosis and prognosis and provided the foundation for the study of the pathogenesis of low-grade glioma.

Analyses of metastasis-associated genes in IDH wild-type glioma.

BACKGROUND: Glioma is the most common malignant tumor of the brain. The existence of metastatic tumor cells is an important cause of recurrence even after radical glioma resection. METHODS: Single-cell sequencing data and high-throughput data were downloaded from GEO database and TCGA/CGGA database. By means of PCA and tSNE clustering methods, metastasis-associated genes in glioma were identified. GSEA explored possible biological functions that these metastasis-associated genes may participate in. Univariate and multivariate Cox regression were used to construct a prognostic model. RESULTS: Glioma metastatic cells and metastasis-associated genes were identified. The prognostic model based on metastasis-associated genes had good sensitivity and specificity for the prognosis of glioma. These genes may be involved in signal pathways such as cellular protein catabolic process, p53 signaling pathway, transcriptional misregulation in cancer and JAK-STAT signaling pathway. CONCLUSION: This study explored glioma metastasis-associated genes through single-cell sequencing data mining, and aimed to identify prognostic metastasis-associated signatures for glioma and may provide potential targets for further cancer research.

Immune-Related lncRNA Risk Signatures Predict Survival of IDH Wild-Type and MGMT Promoter Unmethylated Glioblastoma.

INTRODUCTION: Glioblastoma is the most malignant grade of glioma, and it is also the most common primary tumor in the brain. Immunotherapy is a kind of precise tumor treatment. However, there are limited studies about immune-related lncRNA. This study is aimed at analyzing immune-related lncRNAs in glioblastoma and screening out prognostic factors, providing new potential targets for glioblastoma immunology research. Material and Methods. Gene expression data and clinical data of IDH wild-type with MGMT promoter unmethylated glioblastoma were acquired from the TCGA and CGGA databases. Immune-related lncRNAs were identified with the help of data from the InnateDB database. Immune prognostic factors were recognized by Cox regression analysis. GSEA analysis pursued their potential functions. RESULTS: We found 318 immune-related lncRNAs. Among them, there were 137 immune-related lncRNAs that were upregulated and 181 that were downregulated. 15 prognostic lncRNAs were identified by Cox regression, and a total of 6 molecules were included in the following risk scoring model. GSEA showed that these lncRNAs participated in functions such as protein digestion and absorption and the PPAR signaling pathway. CONCLUSION: There are limited studies about immune regulation mechanisms of lncRNA in IDH wild-type with MGMT promoter unmethylated glioblastoma. The identified immune-related lncRNAs in glioblastoma might contribute new targets and research directions for immunological molecular studies of glioblastoma.

A clinical pathway for pre-operative screening of COVID-19 and its influence on clinical outcome in patients with traumatic fractures.

PURPOSE: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. The toughest issue traumatic orthopaedic surgeons are faced with is how to maintain a balance between adequate COVID-19 screening and timely surgery. In this study, we described our experience with pre-operative COVID-19 screening in patients with traumatic fractures. Furthermore, we analysed the clinical results of fracture patients undergoing confined or emergency surgery during the COVID-19 outbreak. METHODS: This was a case series study. Patients with traumatic fractures who were admitted to our hospital for surgery were enrolled in this study during the COVID-19 outbreak from March to April 2020. All patients were enrolled and managed using the standardized clinical pathway we designed for preoperative COVID-19 screening. Clinical, laboratory and outcome data were analysed. RESULTS: The average surgery waiting time from injury to surgery was 8.7 ± 3.4 days. The average waiting time from admission to surgery was 5.3 ± 2.8 days. These average waiting times were increased by 4.1 days and 2.0 days, respectively, compared with 2019 data. Cardiovascular complications, venous thromboembolism and pneumonia occurred in one, two and one patient, respectively. Three and two patients developed pre-operative and postoperative fevers, respectively. CONCLUSIONS: We introduced a novel clinical pathway for pre-operatively screening of COVID-19 in traumatic orthopaedic patients. The delay in surgery caused by COVID-19 screening was minimized to a point at which reasonable and acceptable clinical outcomes were achieved. Doctors should pay more attention to perioperative complications, such as cardiovascular complications, venous thromboembolism, pneumonia and fever.

Multidirectional percutaneous drilling and autologous bone marrow injection for the treatment of femoral diaphyseal nonunions: a prospective interventional study.

BACKGROUND: To examine the outcomes of multidirectional percutaneous drilling and autologous concentrated bone marrow (BM) transplantation for atrophic femoral diaphyseal nonunion characterized by intact hardware and mechanical stability at the nonunion site. METHODS: Fourteen patients (22-63 years of age) were admitted to our hospital with atrophic femoral diaphyseal nonunion. All patients were treated with a combination of multidirectional percutaneous drilling and autologous concentrated BM transplantation. Radiographic evaluation was conducted every month after transplantation until bone healing was achieved. RESULTS: Bony union was achieved in 13 of the 14 patients (92.9%) after an average of 3.9 months (range: 2.5-6 months). The average radiographic union scale in tibial (RUST) scale score improved significantly from the preoperative period (6.15±1.21) to follow-up (11.23±0.73; P<0.05). The mean follow-up after transplantation was 31.4±9.5 months (range: 18-50 months). At the final follow-up, the quality of function had improved significantly, allowing a return to normal activities. CONCLUSION: Combined multidirectional percutaneous drilling and autologous concentrated BM transplantation is an easy, safe, inexpensive, and efficacious method to treat atrophic femoral diaphyseal nonunion characterized by intact hardware and mechanical stability at the nonunion site.Trial registration number: ISRCTN29808592.

Survival analysis of immune-related lncRNA in low-grade glioma.

BACKGROUND: Low-grade glioma is grade I-II glioma. Immunotherapy is a promising way of tumor killing. Research on immune molecular mechanisms in low-grade gliomas and discovery of new immune checkpoints for low-grade gliomas are of great importance. METHODS: Gene sequencing data and clinical data of low-grade glioma were downloaded from TCGA database. Prognosis related lncRNAs were identified by Cox regression and their possible functions were found by gene enrichment set analysis. RESULTS: A total of 529 low-grade glioma samples and 5 non-tumor brain tissue samples are obtained from the TCGA database. Two hundred forty-seven immune-associated lncRNAs are screened. Cox regression showed that 16 immune-related lncRNAs are associated with low-grade glioma prognosis, and 7 lncRNAs are independent risk factors. Gene set enrichment analysis suggests that these molecules are enriched in extracellular region, sequence-specific DNA binding, neuropeptide signaling pathway, transcriptional misregulation in cancer, cytokine-cytokine receptor interaction, protein digestion and absorption, chemokine signaling pathway, etc. CONCLUSION: The identification of immune-related lncRNA may provide new targets for the research of the molecular mechanisms and treatment of low-grade glioma.

A prognostic nomogram for neuroblastoma in children.

INTRODUCTION: Neuroblastoma is one of the most common extracranial solid tumors in children, which accounts for about 7-10% in children's tumors. The prognosis group of patients with neuroblastoma could not only improve the efficacy of high-risk patients, but also reduce the effects of drug complications for surviving patients. MATERIAL AND METHODS: Patients diagnosed with neuroblastoma between 1986 and 2012 were selected form the TARGET database. The nomogram was built with potential risk factors based on COX regression analysis. The precision of the 3-year and 5-year survival of the nomograms was evaluated by the area under receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 757 child neuroblastoma patients were selected from the TARGET database. Univariate analysis showed that age of diagnosis (>520 day), race of American Indian or Alaska Native, stage 4 in International Neuroblastoma Staging System (INSS), MYCN status, DNA ploidy, and high mitosis-karyorrhexis index were associated with overall survival (OS). Multivariate analysis showed age of diagnosis (>520 day), stage 4 in INSS and DNA ploidy were independent risk factors of OS. The concordance index (C-index) of the nomogram was 0.704 (95% CI [0.686-0.722]) in the training cohort while the C-index in the validation cohort was 0.672 (95% CI [0.644-0.700]). AUC values of ROC curves for 3-year OS and 5-year OS in the training cohort were 0.732 and 0.772, respectively. The nomogram performed better compared with INSS staging system, tumor histology and children's oncology group (COG) risk group with C-indexes of 0.662 (95% CI [0.648-0.676]), 0.637 (95% CI [0.622-0.652]) and 0.651 (95% CI [0.637-0.665]), respectively. CONCLUSIONS: The nomogram showed stronger predictive power than the INSS staging system, tumor histology and COG risk group. Precise estimates of the prognosis of childhood neuroblastoma might help doctors make better treatment decisions.

Visual Contrast Modulates Operant Learning Responses in Larval Zebrafish.

The larval zebrafish is a promising vertebrate model organism to study neural mechanisms underlying learning and memory due to its small brain and rich behavioral repertoire. Here, we report on a high-throughput operant conditioning system for zebrafish larvae, which can simultaneously train 12 fish to associate a visual conditioned pattern with electroshocks. We find that the learning responses can be enhanced by the visual contrast, not the spatial features of the conditioned patterns, highlighted by several behavioral metrics. By further characterizing the learning curves as well as memory extinction, we demonstrate that the percentage of learners and the memory length increase as the conditioned pattern becomes darker. Finally, little difference in operant learning responses was found between AB wild-type fish and elavl3:H2B-GCaMP6f transgenic fish.

A meta-analysis and systematic review evaluating the use of erythropoietin in total hip and knee arthroplasty.

PURPOSE: The debate is still ongoing on the effectiveness and safety of erythropoietin (EPO) treatment in orthopedic surgeries. Specifically, previous studies have not compared the dynamic change of hemoglobin (Hb) levels between different transfusion methods. Besides, complications or side effects of this alternative have not been quantitatively analyzed. We conducted a meta-analysis and systemic review to evaluate the efficacy of EPO on Hb levels observed during the whole perioperative period as well as the volume of allogeneic blood transfusion (ABT), the risk of venous thromboembolism, and application frequency of ABT in hip and knee surgery. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and the Cochrane library were systematically searched from inception to November 2017. The data from randomized controlled trials were extracted and the risk of bias assessed using Cochrane's Collaboration's tool. RESULTS: Twenty-five randomized controlled trials involving 4,159 patients were included in this meta-analysis. EPO could reduce exposure to allogeneic blood transfused (odds ratio [OR] =0.42, P=0.001) and reduce the average volume of allogeneic blood transfused (OR = -0.28, P=0.002). When EPO and preoperative autologous blood donation (PABD) were compared, the use of EPO was associated with lower exposure to ABT (OR =0.48, P=0.03), but no significant decrease in the average volume of allogeneic blood transfused (OR = -0.23, P=0.32). The use of EPO was associated with a higher level of Hb with or without use of PABD at all the 4 time points (preoperation, 24-48 hours postoperation, 3-5 days postoperation, discharge of last observation) (P<0.0001), which means EPO could increase the level of Hb significantly during the perioperative period. The results also indicated EPO does not increase the risk of a venous thromboembolism event. CONCLUSION: Preoperative administration of EPO was shown to generally increase Hb levels during the whole perioperative period; however, the extent of the positive effects varies with time points. Additionally, EPO minimizes the need for transfusion significantly in patients undergoing hip or knee surgery without increasing the chance of developing thrombotic complications. Therefore, EPO offers an alternative blood management strategy in total hip arthroplasty and total knee arthroplasty.