Interpretation of course conceptual structure and student self-efficacy: an integrated strategy of knowledge graphs with item response modeling.

BACKGROUND: There is a scarcity of studies that quantitatively assess the difficulty and importance of knowledge points (KPs) depending on students' self-efficacy for learning (SEL). This study aims to validate the practical application of psychological measurement tools in physical therapy education by analyzing student SEL and course conceptual structure. METHODS: From the "Therapeutic Exercise" course curriculum, we extracted 100 KPs and administered a difficulty rating questionnaire to 218 students post-final exam. The pipeline of the non-parametric Item Response Theory (IRT) and parametric IRT modeling was employed to estimate student SEL and describe the hierarchy of KPs in terms of item difficulty. Additionally, Gaussian Graphical Models with Non-Convex Penalties were deployed to create a Knowledge Graph (KG) and identify the main components. A visual analytics approach was then proposed to understand the correlation and difficulty level of KPs. RESULTS: We identified 50 KPs to create the Mokken scale, which exhibited high reliability (Cronbach's alpha = 0.9675) with no gender bias at the overall or at each item level (p > 0.05). The three-parameter logistic model (3PLM) demonstrated good fitness with questionnaire data, whose Root Mean Square Error Approximation was < 0.05. Also, item-model fitness unveiled good fitness, as indicated by each item with non-significant p-values for chi-square tests. The Wright map revealed item difficulty relative to SEL levels. SEL estimated by the 3PLM correlated significantly with the high-ability range of average Grade-Point Average (p < 0.05). The KG backbone structure consisted of 58 KPs, with 29 KPs overlapping with the Mokken scale. Visual analysis of the KG backbone structure revealed that the difficulty level of KPs in the IRT could not replace their position parameters in the KG. CONCLUSION: The IRT and KG methods utilized in this study offer distinct perspectives for visualizing hierarchical relationships and correlations among the KPs. Based on real-world teaching empirical data, this study helps to provide a research foundation for updating course contents and customizing learning objectives. TRIAL REGISTRATION: Not applicable.

Increased Extracellular Water in Normal-Appearing White Matter in Patients with Cerebral Small Vessel Disease.

BACKGROUND: Microcirculatory variations have been observed in the normal-appearing white matter (NAWM) of individuals affected by cerebral small vessel disease (CSVD). These variations collectively possess the potential to trigger neuroinflammation and edema, ultimately leading to an elevation in extracellular fluid (ECF). Nevertheless, the specific alterations in ECF within the NAWM of CSVD patients have remained inadequately understood. METHODS: We reviewed the clinical and imaging characteristics of a cohort comprising 129 patients diagnosed with CSVD to investigate alterations in the ECF within NAWM. The severity of CSVD was assessed by total CSVD magnetic resonance (MR) score according to the four imaging markers, namely perivascular space, lacunar infarction, white matter hyperintensities and cerebral microbleed. ECF was evaluated by the parameter free water (FW), ranging from 0 to 1 generated from diffusion tensor imaging. RESULTS: Significant differences in NAWM FW were observed in relation to the total CSVD MR score (p < 0.05). Patients with a total CSVD MR score of 0 exhibited significantly lower NAWM free water (FW) values compared to those with a score greater than 0 (p < 0.05). Similarly, patients with a total CSVD MR score of 1 also demonstrated notably lower NAWM FW values than those with a score greater than 1 (p < 0.05). After conducting multivariate regression analysis, age and total CSVD MR score was independently associated with FW in NAWM (p < 0.001). Further, the total CSVD MR score served as a partial mediator in the relationship between age and FW in the NAWM among patients with CSVD. CONCLUSIONS: ECF in NAWM is increased in CSVD patients, even during the early course of CSVD.

Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.

CircRNA ARHGAP10 promotes osteogenic differentiation through the miR-335-3p/RUNX2 pathway in aortic valve calcification.

Background: Calcific aortic valve disease (CAVD) is a common cardiovascular disease with high morbidity and mortality, and no effective prevention or treatment is available. In recent years, increasing evidence has shown that noncoding RNAs (ncRNAs) play an important role in the pathogenesis and prognosis of CAVD. Several associated circular RNAs (circRNAs) have been reported to be involved in CAVD, such as circRIC3 and TGFBR2. However, the limited number of circRNAs identified in CAVD warrants further in-depth investigation, and the comprehensive elucidation of their role in the key mechanisms of this disease is needed. Methods: The expression of circRNAs and microRNAs (miRNAs) were analyzed by RNA sequencing. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the expression of circRNA ARHGAP10 (circARHGAP10), miR-335-3p, and RUNX2. Luciferase reporter assay, pull-down assay, and RNA binding protein immunoprecipitation (RIP) assay were performed to evaluate the binding of miR-335-3p to circARHGAP10 or RUNX2. Alizarin red S staining showed the formation of calcified nodules in valve interstitial cells (VICs). The expression of circARHGAP10 and miR-335-3p was altered through lentivirus infection. Alkaline phosphatase (ALP) activity was used to verify the correlation between circARHGAP10 and miR-335-3p. The expression of proteins was assessed via Western blot. RNA fluorescence in situ hybridization (FISH) was used to confirm the localization of circARHGAP10 in the cytoplasm of VICs. Immunofluorescence was used to detect the expression level of RUNX2. ApoE-/- mice were used to construct a CAVD model, circARHGAP10 short hairpin RNA (shRNA) and miR-335-3p inhibitor lentivirus were intraperitoneally injected, and scramble and inhibitor normal control (NC) lentivirus were injected as controls, followed by hematoxylin and eosin (HE) staining. Results: Through RNA sequencing, we found that circARHGAP10 (hsa_circ_0008975) was highly expressed in calcific aortic valves. CircARHGAP10 knockdown effectively inhibited the extent of osteogenic differentiation of VICs. We then found that circARHGAP10 was a competing endogenous RNA (ceRNA) of miR-355-3p and that miR-355-3p targeted RUNX2. In vitro experiments confirmed that circARHGAP10 regulated the osteogenic differentiation of VICs through the miR-355-3p/RUNX2 pathway, and this was validated in vivo using an ApoE-/- mouse model. Conclusions: These findings provide a foundation for circRNA-directed diagnostics and therapeutics for CAVD.

Role of miR-5010-3p in predicting the prognosis of hepatocellular carcinoma. / MiR-5010-3p在预测肝细胞癌预后中的作用（英文）.

OBJECTIVES: Numerous miRNAs have been found to be abnormally expressed in hepatocellular carcinoma (HCC). However, clinical significance of miR-5010-3p in HCC is not elucidated. This study aims to explore the prognostic value and role of miR-5010-3p in HCC. METHODS: The differential gene expression analysis of miR-5010-3p in HCC was performed based on the Cancer Genome Atlas (TCGA) database. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of miR-5010-3p expression level for HCC prognosis. The Kaplan-Meier, Cox univariate, and Cox multivariate analysis were used to predict its role in the prognosis of HCC. The downstream target genes were predicted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the potential functional pathways they may participate in. Finally, methyl thiazolyl tetrazolium (MTT) assay and 5-ethyl-2'-deoxyuridine (EDU) incorporation experiment were carried out to prove its effect on proliferation. RESULTS: The expression of miR-5010-3p was associated with histological grade (P=0.019), vascular invasion degree (P=0.049), TP53 level (P=0.004), and alpha fetoprotein (AFP) level (P=0.012). A moderate ability to distinguish between tumor and paracancerous tissues of miR-5010-3p in HCC was perceived by ROC curve (AUC: 0.712, 95% CI 0.649 to 0.776). High expression of miR-5010-3p was associated with shorter overall survival (OS) (P=0.003). The results of functional enrichment analysis showed that miR-5010-3p was related to the tumorigenesis process. In vitro experiments verified that miR-5010-3p promoted the proliferation of hepatocellular carcinoma cells. CONCLUSIONS: MiR-5010-3p promotes the proliferation of liver cancer cells, and its high expression is associated with poor prognosis, which may be a potential prognostic marker.

Mechanism underlying the effect of Pulsatilla decoction in hepatocellular carcinoma treatment: a network pharmacology and in vitro analysis.

BACKGROUND: Currently, hepatocellular carcinoma (HCC) is associated with a poor prognosis. Moreover, there exist limited strategies for treating HCC. Pulsatilla decoction (PD), a traditional Chinese medicine formula, has been used to treat inflammatory bowel disease and several cancer types. Accordingly, we explored the mechanism of PD in HCC treatment via network pharmacology and in vitro experiments. METHODS: Online databases were searched for gene data, active components, and potential target genes associated with HCC development. Subsequently, bioinformatics analysis was performed using protein-protein interaction and Network Construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) to screen for potential anticancer components and therapeutic targets of PD. Finally, the effect of PD on HCC was further verified by in vitro experiments. RESULTS: Network pharmacological analysis revealed that 65 compounds and 180 possible target genes were associated with the effect of PD on HCC. These included PI3K, AKT, NF-κB, FOS, and NFKBIA. KEGG analysis demonstrated that PD exerted its effect on HCC mainly via the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments revealed that PD could significantly inhibit cancer cell proliferation and kill HCC cells by inducing apoptosis. Furthermore, western blotting confirmed that apoptosis was mediated primarily via the PI3K-AKT, IL-17, and TNF signaling pathways. CONCLUSION: To the best of our knowledge, this is the first study to elucidate the molecular mechanism and potential targets of PD in the treatment of HCC using network pharmacology.

Cations facilitate sulfidation of zero-valent iron by elemental sulfur: Mechanism and dechlorination application.

The solid-solid reaction of microscale zero-valent iron (mZVI) with elemental sulfur (S0) in water can form sulfidated mZVI (S-mZVI) with high reactivity and selectivity. However, the inherent passivation layer of mZVI hinders the sulfidation. In this study, we demonstrate that ionic solutions of Me-chloride (Me: Mg2+, Ca2+, K+, Na+ and Fe2+) can accelerate the sulfidation of mZVI by S0. The S0 with S/Fe molar ratio of 0.1 was fully reacted with mZVI in all solutions to form unevenly distributed FeS species on S-mZVIs as confirmed by SEM-EDX and XANES characterization. The cations depassivated the mZVI surface by driving the proton release from the surface site (FeOH) and resulting in localized acidification. The probe reaction test (tetrachloride dechlorination) and open circuit potential (EOCP) measurement demonstrated that Mg2+ was most efficient in depassivating the mZVI and therefore promoting sulfidation. The decrease of surface proton for hydrogenolysis on the S-mZVI synthesized in MgCl2 solution also inhibited the formation of cis-1,2-dichloroethylene by 14-79% compared to other S-mZVIs during trichloroethylene dechlorination. In addition, the synthesized S-mZVIs exhibited the highest reduction capacity reported so far. These findings provide a theoretical basis for the facile on-site sulfidation of mZVI by S0 with cation-rich natural waters for sustainable remediation of contaminated sites.

Integrated pan-cancer analysis of centromere protein F and experimental verification of its role and clinical significance in cholangiocarcinoma.

Centromere protein F (CENPF), a protein related to the cell cycle, is a key part of the kinetochore-centromere complex involved in cell division, differentiation, and proliferation. CENPF expression is upregulated in various types of cancer and plays a role in oncogenesis and tumor progression. However, the expression pattern, prognostic significance, and biological role of CENPF in these cancer types are poorly understood. Therefore, in this study, we conducted a pan-cancer analysis of the role of CENPF, which we considered a cut point, to investigate its utility as a prognostic and immunological indicator for malignancies, especially cholangiocarcinoma (CCA). Using systematic bioinformatics analysis, we investigated the expression patterns, prognostic relevance, molecular function, signaling pathways, and immune infiltration patterns of CENPF in the pan-cancer analysis. Western blot and immunohistochemistry staining assays were performed to evaluate the expression profiles of CENPF in CCA tissues and cell lines. Furthermore, Cell Counting Kit-8, colony formation, wound healing, and Transwell assays, as well as CCA xenograft mouse models, were employed to determine the role and function of CENPF in CCA. The results showed that CENPF expression was upregulated and strongly linked to a worse prognosis in most cancer types. CENPF expression was substantially associated with immune cell infiltration, tumor microenvironment, genes related to immune checkpoints, tumor mutational burden, microsatellite instability, and immunotherapy response in diverse malignancies. CENPF was considerably overexpressed in CCA tissues and cells. Functionally, inhibiting CENPF expression significantly reduced the proliferating, migrating, and invading abilities of CCA cells. CENPF expression also affects the prognosis of multiple malignancies, which is highly associated with immunotherapy response and tumor immune cell infiltration. In conclusion, CENPF may act as an oncogene and an immune infiltration-related biomarker and can accelerate tumor development in CCA.

Enhanced removal of hexavalent chromium by lignosulfonate modified zero valent iron: Reaction kinetic, performance and mechanism.

The application of lignin derivative as modifier is an economical and efficient approach to improve the reactivity of raw material towards pollutant removal. In this study, lignosulfonate modified zero valent iron (LS-ZVI) was firstly prepared by ball-milling method and utilized for Cr(VI) removal under different conditions. The comparative experiments showed that lignosulfonate modification could significantly enhance the Cr(VI) removal by ZVI from <10 % to 100 % within 90 min reaction. Compared to ZVI, the specific surface area of LS-ZVI increased 3.4 times and surface Fe(0) content increased from 3.4 % to 10.5 % due to the surface erosion, resulting in the high-efficient Cr(VI) removal. Solution and solid-phase analyses indicated that Fe(0) played dominated role and generated Fe(II) involved in Cr(VI) removal process, which mainly included rapid adsorption, reduction and co-precipitation. Batch experiments revealed that lower pH conditions were beneficial for Cr(VI) removal and the effect of co-existing ions (Ca2+, Mg2+, NO3-, Cl-, and SO42-) was negligible except the inhibitory effect of NO3-. Moreover, LS-ZVI also exhibited excellent removal performance for Ni(II), Zn(II), and Cd(II) with removal efficiency beyond 96.6 %. Overall, this work provides a feasible approach for enhancing the reactivity of commercial ZVI in the treatment of heavy metal pollution.

Impact of Decreased Visibility of Deep Medullary Veins on White Matter Integrity in Patients with Cerebral Small Vessel Disease.

BACKGROUND: Based on susceptibility-weighted imaging (SWI) visibility, deep medullary vein (DMV) scores are related to white matter damage (WMD) in patients with cerebral small vessel disease (CSVD). However, whether mechanisms are associated with DMV changes is unclear. We examined extracellular fluid (ECF) roles in white matter associations between DMV scores and white matter integrity (WMI) in patients with CSVD. METHODS: We examined magnetic resonance imaging (MRI) and clinical data from 140 patients with CSVD. DMV scores (0-18) were assigned on SWI according to DMV anatomic regions and signal continuity/visibility. WMI and ECF volumes were evaluated using free water (FW) and fractional anisotropy (FA) values by diffusion tensor imaging (DTI). RESULTS: DMV scores were independently associated with FA after adjusting for vascular risk factors, age, white matter hyperintensity (WMH) volume, and CSVD burden [ß (95% confidence interval (CI)): -0.219 (-0.375, -0.061), p = 0.006]. We also observed a significant indirect effect of DMV scores on FA in white matter (mediated by FW in white matter) after controlling for age, vascular risk factors, WMH volume, and CSVD burden. CONCLUSIONS: DMV scores were independently related to WMI and mediated by ECF in the white matter of patients with CSVD.

TRPM8 contributes to liver regeneration via mitochondrial energy metabolism mediated by PGC1α.

Impairment of liver regeneration leads to severe morbidity in acute and chronic severe liver disease. Transient receptor potential melastain 8 (TRPM8) is involved in a variety of processes, including temperature sensing, ion homeostasis, and cell proliferation. However, whether TRPM8 contributes to liver regeneration is still unclear. We assessed the effect and mechanism of TRPM8 in liver regeneration and hepatocyte proliferation in vivo and in vitro. In this study, we found that TRPM8 deficiency impairs liver regeneration in mice. Mechanistically, the results revealed that mitochondrial energy metabolism was attenuated in livers from TRPM8 knockout (KO) mice. Furthermore, we found that TRPM8 contributes to the proliferation of hepatocytes via PGC1α. Taken together, this study shows that TRPM8 contributes to liver regeneration in mice after hepatectomy. Genetic approaches and pharmacological approaches to regulate TRPM8 activity may be beneficial to the promotion of liver regeneration.

The hypoxia-related signature predicts prognosis, pyroptosis and drug sensitivity of osteosarcoma.

Osteosarcoma (OS) is one of the most common types of solid sarcoma with a poor prognosis. Solid tumors are often exposed to hypoxic conditions, while hypoxia is regarded as a driving force in tumor recurrence, metastasis, progression, low chemosensitivity and poor prognosis. Pytoptosis is a gasdermin-mediated inflammatory cell death that plays an essential role in host defense against tumorigenesis. However, few studies have reported relationships among hypoxia, pyroptosis, tumor immune microenvironment, chemosensitivity, and prognosis in OS. In this study, gene and clinical data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases were merged to develop a hypoxia risk model comprising four genes (PDK1, LOX, DCN, and HMOX1). The high hypoxia risk group had a poor prognosis and immunosuppressive status. Meanwhile, the infiltration of CD8+ T cells, activated memory CD4+ T cells, and related chemokines and genes were associated with clinical survival outcomes or chemosensitivity, the possible crucial driving forces of the OS hypoxia immune microenvironment that affect the development of pyroptosis. We established a pyroptosis risk model based on 14 pyroptosis-related genes to independently predict not only the prognosis but also the chemotherapy sensitivities. By exploring the various connections between the hypoxic immune microenvironment and pyroptosis, this study indicates that hypoxia could influence tumor immune microenvironment (TIM) remodeling and promote pyroptosis leading to poor prognosis and low chemosensitivity.

Effects of Qigong Therapy on the Anaerobic Threshold in Patients with Stable Coronary Artery Disease: A Randomized Controlled Trial.

Objective: This study aims to identify whether Qigong (QG) rehabilitation therapy can significantly improve the cardiac function of patients with stable coronary artery disease (SCAD) compared with routine therapy. Thus, a randomized controlled trial was conducted to evaluate the curative effects of a three-month QG rehabilitation therapy on cardiac rehabilitation. Patients and Methods. In this trial, a total of 68 patients with SCAD were randomly divided into the QG group (34 patients) and the control (CON) group (34 patients). Patients in the CON group received routine cardiologic medication without any special intervention. Based on the treatment in the CON group, patients in the QG group were provided additionally with a 12-week traditional Chinese medicine (TCM) cardiac rehabilitation QG exercise training program. The outcomes of these patients were assessed at baseline and after 12 weeks of intervention through the treadmill (anaerobic threshold (AT)) test. Results: After 12 weeks of intervention, the AT, volume of oxygen (VO2), oxygen uptake/kilogram (VO2/kg), metabolic equivalents (METS), and oxygen pulse (VO2/HR) of patients in the QG group were significantly higher than those of patients in the CON group (P < 0.05). Conclusion: QG therapy can achieve certain curative effects and safety for patients with SCAD. This trial is registered with Clinicaltrials.gov identifier (ChiCTR1800015823).

Transient Receptor Potential Vanilloid-1 (TRPV1) Alleviates Hepatic Fibrosis via TGF-ß Signaling.

Hepatic fibrosis is a major global health problem and considered a leading cause of liver-related morbidity and mortality worldwide. Although previous studies have suggested that transient receptor potential vanilloid-1 (TRPV1) is protective against cardiac and renal fibrosis, its functional role in hepatic fibrosis has remained elusive. Herein, we characterize the effects of TRPV1 on carbon tetrachloride- (CCl4-) induced mice, in vitro transforming growth factor-ß- (TGF-ß-) treated hepatic stellate cells (HSCs), and human fibrosis specimens. Finally, our results demonstrated the significant TRPV1 downregulation in human liver fibrosis tissues. Knocking out TRPV1 significantly increased the expression of various hepatic fibrosis markers, while the expression of these biomarkers declined markedly in capsaicin-activated mice. Moreover, our study revealed that knocking down TRPV1 would enhance the promotive effect of TGF-ß on HSC proliferation, cell cycle, cell apoptosis, and ECM expression. Also, such promotive effect can be partially reversible by capsaicin, an exogenous activator of TRPV1. Collectively, the obtained data suggest that TRPV1 may alleviate CCl4-induced hepatic fibrosis and attenuate the effect of TGF-ß on HSC activation, proliferation, and apoptosis, which overall implies that targeting TRPV1 channel activity may be an effective therapeutic strategy for treating hepatic fibrosis.

TRPM8 deficiency attenuates liver fibrosis through S100A9-HNF4α signaling.

BACKGROUND: Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis. METHODS: The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8-/- (KO) fibrotic mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments. RESULTS: Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl4- and BDL- treated TRPM8-/- mice. A strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells that underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, the alleviative effect of a selective TRPM8 antagonist was confirmed in vivo. CONCLUSIONS: These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis.

Identification of two immune-related risk score signatures through integrated analysis of multi-omics data in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Immunotherapy has become a major treatment for advanced HCC, but the therapeutic effects remain unsatisfactory. In this study, we constructed an immune cell risk score (ICS) and an immune cell-related gene risk score (ICRGS) for the prognosis prediction of HCC through integrated analysis of bulk and single-cell RNA (scRNA) sequencing data. These two risk score signatures both showed good predictive values in the training and validation cohorts. The potential interactions among these prognostic immune cell types were elucidated by cell-cell communication analysis. The results of enrichment analysis and gene set enrichment analysis (GSEA) of the prognostic genes showed that metabolic-related processes were involved in the immune response of HCC. Furthermore, the results of correlation analyses further confirmed the hub genes that were strongly correlated with immune cells. Finally, potential therapeutic drugs targeting these hub genes were screened by CellMiner based on NCI-60 cell line set. Taken together, two useful models for the prognosis prediction of HCC patients were constructed in this study. The functional differences between the two groups of HCC patients separated by ICS or ICRGS provide fundamental knowledge for finding synergistic therapeutic targets for HCC immunotherapy.

Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers.

BACKGROUND: The cumulative risk of distant recurrence of hormone receptor-positive (HR+) breast cancer in the past 20 years has ranged from 22% to 52% after 5 years of endo-therapy. The TNM stage, histological grade, and age are important clinical factors related to recurrence, however the exact mechanism of tamoxifen resistance is still unclear. METHODS: Differentially expressed genes (DEGs) were identified in 10 pairs of patients who had relapsed and non-relapsed after tamoxifen treatment based on matching their clinicopathological factors. After analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 10 hub genes were identified using Cytoscape software. Next, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used to verify the expression and overall survival (OS) of the 10 hub genes respectively, and GSE96058 and Kaplan-Meier Plotter website were used to further verify the OS of C3, CX3CL1, CXCL2, and SAA1. Finally, Immune Cell Abundance Identifier (ImmuCellAI) and the TIMER database were used to estimate immune cell infiltration and the expression of prognostic genes. RESULTS: The DEGs were mainly enriched in the inflammatory response and cytokine-receptor interaction. The expression and the survival analysis identified CX3CL1, CXCL2, and SAA1 as prognostic factors, whose overexpression in HR+/human epidermal growth factor receptor 2 (HER-2) negative breast cancer possibly predicted a longer disease-free survival. The expression levels of these 3 genes are positively correlated with immune cell infiltration. Their high expression levels may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be biomarkers for tamoxifen-resistant therapy. CONCLUSIONS: In conclusion, the high expression of CX3CL1, CXCL2, and SAA1 may predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.

NaFe2PO4(MoO4)2: A Promising NASICON-Type Electrode Material for Sodium-Ion Batteries.

Searching for polyanionic electrode materials with high Na+ and electronic conductivity is pivotal to realize high-performance sodium-ion batteries. Here, we report a novel polyanionic-based NASICON-type compound, NaFe2PO4(MoO4)2 (NFPM), that does not crystallize in the common space group R-3c or C2/c but in the rare P2/c. The studies on bond valence sum maps show that NFPM has high Na+ conductivity because the large volumes of MoO4 groups make the interstitial channels wider, thus making the energy barrier of Na+ diffusion decrease along these channels. Density functional theory calculations demonstrate that NFPM has high electronic conductivity because the contribution of Mo 4d orbitals on the formation of the bottom of the conduction band makes the connected MoO4 groups take part in electron transport. Electrochemical tests exhibit that NFPM can deliver a capacity of ∼80 mAh g-1 with good reversible cyclability utilizing the Fe3+/Fe2+ redox couple. In situ X-ray diffraction measurements indicate that NFPM undergoes one-phase reaction mechanism in the process of charge and discharge.

Brachial plexus injury after clavicle fracture operation: a case report and literature review.

BACKGROUND: Open reduction and internal fixation (ORIF) is the preferred choice for treating clavicle fractures. The brachial plexus injury caused by ORIF of a clavicle fracture is very rare. If it is not treated in time, the function of the brachial plexus will be challenging to recover, which will eventually lead to upper limb dysfunction and seriously affect the patient's quality of life. Our team recently used ORIF to treat a patient with a clavicle fracture, who developed brachial plexus injury symptoms after surgery. CASE PRESENTATION: A 34-year-old female patient was admitted to the hospital for 13 h due to the right shoulder movement restriction after a fall. Due to the significant displacement of the fracture, we used ORIF to treat the fracture. The surgery went well. When the anaesthesia effect subsided 12 h after the operation, the patient developed right brachial plexus injury symptoms, decreased right upper limb muscle strength, dysfunction, and hypoesthesia. Symptomatic treatments, such as nourishing nerve and electrical stimulation, were given immediately. Sixty days after the operation, the patient's brachial plexus injury symptoms disappeared, and the function of the right upper limb returned to the preoperative state. CONCLUSIONS: Patients with clavicle fractures usually need to undergo a careful physical examination before surgery to determine whether symptoms of brachial plexus injury have occurred. Anaesthesia puncture requires ultrasound guidance to avoid direct damage to the brachial plexus. When the fracture end is sharp, reset should be careful to prevent nerve stump stabbed. When using an electric drill to drill holes, a depth limiter should be installed in advance to prevent the drill from damaging the subclavian nerve and blood vessels. When measuring the screw depth, the measuring instrument should be close to the bone surface and sink slowly to avoid intense hooks and damage to the brachial plexus. Try to avoid unipolar electrosurgical units to prevent heat conduction from damaging nerves, and bipolar electrocoagulation should be used instead. If symptoms of brachial plexus injury occur after surgery, initial symptomatic treatment is drugs and functional exercise, and if necessary, perform surgical exploration.