Quantitative Benefit-Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial.

BACKGROUND: The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches. METHODS AND RESULTS: Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation. CONCLUSIONS: These analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.

Artificial Heterointerfaces with Regulated Charge Distribution of Ni Active Sites for Urea Oxidation Reaction.

In contrast to the thermodynamically unfavorable anodic oxygen evolution reaction, the electrocatalytic urea oxidation reaction (UOR) presents a more favorable thermodynamic potential. However, the practical application of UOR has been hindered by sluggish kinetics. In this study, hierarchical porous nanosheet arrays featuring abundant Ni-WO3 heterointerfaces on nickel foam (Ni-WO3/NF) is introduced as a monolith electrode, demonstrating exceptional activity and stability toward UOR. The Ni-WO3/NF catalyst exhibits unprecedentedly rapid UOR kinetics (200 mA cm-2 at 1.384 V vs. RHE) and a high turnover frequency (0.456 s-1), surpassing most previously reported Ni-based catalysts, with negligible activity decay observed during a durability test lasting 150 h. Ex situ X-ray photoelectron spectroscopy and density functional theory calculations elucidate that the WO3 interface significantly modulates the local charge distribution of Ni species, facilitating the generation of Ni3+ with optimal affinity for interacting with urea molecules and CO2 intermediates at heterointerfaces during UOR. This mechanism accelerates the interfacial electrocatalytic kinetics. Additionally, in situ Fourier transform infrared spectroscopy provides deep insights into the substantial contribution of interfacial Ni-WO3 sites to UOR electrocatalysis, unraveling the underlying molecular-level mechanisms. Finally, the study explores the application of a direct urea fuel cell to inspire future practical implementations.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Artesunate Alleviates Kidney Fibrosis in Type 1 Diabetes with Periodontitis Rats via Promoting Autophagy and Suppression of Inflammation.

To explore the effect of periodontal disease on the progression of diabetic kidney disease (DKD), to observe the effects of artesunate (ART) intervention on periodontal and kidney tissues in type 1 diabetic rats with periodontitis, and to explore the possibility of ART for the treatment of DKD. Rat models of diabetes mellitus, periodontitis, and diabetes mellitus with periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, and P. gingivalis ligation applied sequentially. Ten weeks after modeling, ART gavage treatment was given for 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to investigate the inflammatory factors, fibrogenisis, autophagy-related factors, and proteins in periodontal and kidney tissues, and 16S rDNA sequencing was used to detect the changes in dental plaque fluid and kidney tissue flora. Compared to the control group, the protein expression levels of transforming growth factor ß1 (TGF-ß1) and COL-IV in the periodontal disease (PD) group were increased. The protein expression of TGF-ß1, Smad3, and COL-IV increased in the DM group and the DM + PD group, and the expression of TGF-ß1, Smad3, and COL-IV was upregulated in the DM + PD group. These results suggest that periodontal disease enhances renal fibrosis and that this process is related to the TGF-ß1/Smad/COL-IV signaling pathway. Among the top five dominant bacteria in the kidney of the DM + PD group, the abundance of Proteobacteria increased most significantly, followed by Actinobacteria and Firmicutes with mild increases. The relative abundance of Proteobacteria, Actinobacteria, and Firmicutes in the kidney tissues of DM and PD groups also showed an increasing trend compared with the CON group. Proteobacteria and Firmicutes in the kidney of the PD group and DM + PD group showed an increasing trend, which may mediate the increase of oxidative stress in the kidney and promote the occurrence and development of DN. Periodontal disease may lead to an imbalance of renal flora, aggravate renal damage in T1DM, cause glomerular inflammation and renal tubulointerstitial fibrosis, and reduce the level of autophagy. ART delays the process of renal fibrosis by inhibiting the TGF-ß-Smad signaling pathway.

Self-Catalyzed Synthesis of Length-Controlled One-Dimensional Nickel Oxide@N-Doped Porous Carbon Nanostructures from Metal Ion Modified Nitrogen Heterocycles for Efficient Lithium Storage.

Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.

[The Effect of TCP1 Expression on the Proliferation and the Accumulation of Intracellular Drug of HL60/A and HL60 Cell and Its Mechanism].

OBJECTIVE: To investigate the effect of TCP1 expression on the proliferation and the accumulation of intracellular drug of HL60/A and HL60 cells and its possible molecular mechanism. METHODS: Lentiviral transfection technology was used to construct HL60/A and HL60 cells with knocked down or overexpressed TCP1 and their control cells. The efficiency of knockdown and overexpression was evaluated by Western blot. The cell proliferation was detected by CCK-8 assay. The intracellular drug accumulation was detected by laser confocal detection and flow cytometry. The expression levels of MRP1, P-gP and p-AKT were evaluated by flow cytometry and Western blot. RESULTS: After TCP1 was knocked down,the proliferation ability of HL60/A cells was significantly reduced, the accumulation of intracellular drug was significantly increased and the expression of MRP1 and P-gP protein were decreased. After TCP1 was overexpressed, the proliferation ability of HL60 was significantly increased, the accumulation of intracellular drug was significantly decreased and the expression of MRP1 and P-gP protein were increased. Intervention of LY294002 significantly antagonized the promotion on cell proliferation, the inhibition on intracellular drug accumulation and the expression of MRP1 and P-gP mediated by TCP1 overexpressing in HL60 cells. CONCLUSION: TCP1 can promote cell proliferation, improve the expression of MRP1 and P-gP by activating PI3K/AKT signal, and reduce intracellular drug accumulation.

A rapid method for identification of Lanxangia tsaoko origin and fruit shape: FT-NIR combined with chemometrics and image recognition.

Lanxangia tsaoko's accurate classifications of different origins and fruit shapes are significant for research in L. tsaoko difference between origin and species as well as for variety breeding, cultivation, and market management. In this work, Fourier transform-near infrared (FT-NIR) spectroscopy was transformed into two-dimensional and three-dimensional correlation spectroscopies to further investigate the spectral characteristics of L. tsaoko. Before building the classification model, the raw FT-NIR spectra were preprocessed using multiplicative scatter correction and second derivative, whereas principal component analysis, successive projections algorithm, and competitive adaptive reweighted sampling were used for spectral feature variable extraction. Then combined with partial least squares-discriminant analysis (PLS-DA), support vector machine (SVM), decision tree, and residual network (ResNet) models for origin and fruit shape discriminated in L. tsaoko. The PLS-DA and SVM models can achieve 100% classification in origin classification, but what is difficult to avoid is the complex process of model optimization. The ResNet image recognition model classifies the origin and shape of L. tsaoko with 100% accuracy, and without the need for complex preprocessing and feature extraction, the model facilitates the realization of fast, accurate, and efficient identification.

Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants.

Importance: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. Objective: To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. Design, Setting, and Participants: In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. Main Outcomes and Measures: The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. Results: A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. Conclusions and Relevance: In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.

Incorporating Prior Data in Quantitative Benefit-Risk Assessments: Case Study of a Bayesian Method.

BACKGROUND: Multiple criteria decision analysis (MCDA) and stochastic multi-criteria acceptability analysis (SMAA) in their current implementation cannot incorporate prior or external information on benefits and risks. We demonstrate how to incorporate prior data using a Bayesian mixture model approach while conducting quantitative benefit-risk assessments (qBRA) for medical products. METHODS: We implemented MCDA and SMAA in a Bayesian framework. To incorporate information from a prior study, we use mixture priors on each benefit and risk attribute that mixes information from a previous study with a vague prior distribution. The degree of borrowing is varied using a mixing proportion parameter. RESULTS: A demonstration case study for qBRA using the supplementary New Drug Application (sNDA) filing for Rivaroxaban for the indication of reduction in the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD) was used to illustrate the method. Net utility scores, obtained from the randomized controlled trial data to support the sNDA, from the MCDA for Rivaraxoban and comparator were 0.48 and 0.56, respectively, with Rivaroxaban being the preferred alternative only 33% of the time. We show that with only 30% borrowing from a previous RCT, the MCDA and SMAA results are favorable for Rivaroxaban, accounting for the seemingly aberrant results on all-cause death in the trial data used to support the sNDA. CONCLUSION: Our method to formally incorporate prior data in MCDA and SMAA is easy to use and interpret. Software in the form of an RShiny App is available here: https://sai-dharmarajan.shinyapps.io/BayesianMCDA_SMAA/ .

Epidemiological characteristics and distribution of pediatric supracondylar fractures in South China: a retrospective analysis of 760 cases.

To evaluate demographic characteristics and distribution of pediatric supracondylar fractures (SCFs) at a tertiary hospital in South China. A retrospective observational study was conducted on children aged 15 years or younger with a diagnosis of SCFs during the period from January 2016 to December 2018. Patients' medical records and radiographs were retrospectively analyzed for age at the time of injury, sex, site and mechanism of traumatic injury. A total of 760 patients with 761 SCFs were reviewed (453 males, 59.6%, and 307 females, 40.4%). There were 748 extension-type fractures (98.3%) and 13 flexion-type fractures (1.7%). Associated injuries were identified in 30/760 (3.9%) patients: associated fracture ( n  = 15; 2%), nerve injury ( n  = 12; 1.6%), open fracture ( n  = 2; 0.2%) and compartment syndrome ( n  = 1; 0.1%). Age at the time of fracture has a bimodal pattern with a first peak around the age of 1 year and a second peak around the age of 4-5 years. The fractures occurred mostly around 11 a.m. and between 4 and 9 p.m. in the evening. Most fractures occurred at home (50.7%), and falling down (62.2%) was the most frequent mechanism of injury. SCFs occurred most frequently in children aged 1 and 4-5 years, and during daylight hours. In about 96% of cases, these were isolated injuries, and falling down was found to be the most frequent traumatic mechanism. Based on our findings, targeted educational efforts and interventions can be set up in order to prevent the occurrence of SCFs in South China. Level of evidence: III.

Isoquercitrin attenuates the progression of non-alcoholic steatohepatitis in mice by modulating galectin-3-mediated insulin resistance and lipid metabolism.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear. PURPOSE: This study was aimed at investigating the effects of IQ on NASH and deciphering whether the underlying mechanisms are via modulation of galectin-3 mediated IR and lipid metabolism. METHODS: IR-HepG2 cell lines were used to demonstrate the ability of IQ to modulate galectin-3-mediated glucose disposal and lipid metabolism. A 20-week high-fat diet (HFD)-induced NASH model was established in C57BL/6J mice, and the protective effect of IQ on lipid disposal in the liver was verified. Further, the mRNA and protein levels of glucose and lipid metabolism were investigated, and lysophosphatidylcholine (LPC) and acylcarnitine (AC) profiling were performed to characterize the changes in endogenous substances associated with mitochondrial function and lipid metabolism in serum and cells. Furthermore, the pharmacokinetic features of IQ were explored in a rat model of NASH. RESULTS: IQ restored liver function and ameliorated inflammation and lipid accumulationin NASH model mice. Notably, significant regulation of the proteins included fatty acid-generating and transporting, cholesterol metabolism enzymes, nuclear transcription factors, mitochondrial metabolism, and IR-related enzymes was noted to be responsible for the therapeutic mechanisms of IQ against experimental NASH. Serum lipid metabolism-related metabolomic assay confirmed that LPC and AC biosynthesis mostly accounted for the therapeutic effect of IQ in mice with NASH and that IQ maintained the homeostasis of LPC and AC levels. CONCLUSION: This is the first study showing that IQ protects against of NASH by modulating galectin-3-mediated IR and lipid metabolism. The mechanisms responsible for liver protection and improved lipid metabolic disorder by IQ may be related to the suppression of IR and regulation of mitochondrial function and lipid metabolism. Galectin-3 down-regulation represents a potentially novel approach for the treatment and prevention of NASH.

Rechargeable Zinc-Air Batteries: Advances, Challenges, and Prospects.

Rechargeable zinc-air batteries (Re-ZABs) are one of the most promising next-generation batteries that can hold more energy while being cost-effective and safer than existing devices. Nevertheless, zinc dendrites, non-portability, and limited charge-discharge cycles have long been obstacles to the commercialization of Re-ZABs. Over the past 30 years, milestone breakthroughs have been made in technical indicators (safety, high energy density, and long battery life), battery components (air cathode, zinc anode, and gas diffusion layer), and battery configurations (flexibility and portability), however, a comprehensive review on advanced design strategies for Re-ZABs system from multiple angles is still lacking. This review underscores the progress and strategies proposed so far to pursuit the high-efficiency Re-ZABs system, including the aspects of rechargeability (from primary to rechargeable), air cathode (from unifunctional to bifunctional), zinc anode (from dendritic to stable), electrolytes (from aqueous to non-aqueous), battery configurations (from non-portable to portable), and industrialization progress (from laboratorial to practical). Critical appraisals of the advanced modification approaches (such as surface/interface modulation, nanoconfinement catalysis, defect electrochemistry, synergistic electrocatalysis, etc.) are highlighted for cost-effective flexible Re-ZABs with good sustainability and high energy density. Finally, insights are further rendered properly for the future research directions of advanced zinc-air batteries.

Enabling Internal Electric Field in Heterogeneous Nanosheets to Significantly Accelerate Alkaline Hydrogen Electrocatalysis.

Efficient bifunctional hydrogen electrocatalysis, encompassing both hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR), is of paramount significance in advancing hydrogen-based societies. While non-precious-metal-based catalysts, particularly those based on nickel (Ni), are essential for alkaline HER/HOR, their intrinsic catalytic activity often falls short of expectations. Herein, an internal electric field (IEF) strategy is introduced for the engineering of heterogeneous nickel-vanadium oxide nanosheet arrays grown on porous nickel foam (Ni-V2 O3 /PNF) as bifunctional electrocatalysts for hydrogen electrocatalysis. Strikingly, the Ni-V2 O3 /PNF delivers 10 mA cm-2 at an overpotential of 54 mV for HER and a mass-specific kinetic current of 19.3 A g-1 at an overpotential of 50 mV for HOR, placing it on par with the benchmark 20% Pt/C, while exhibiting enhanced stability in alkaline electrolytes. Density functional theory calculations, in conjunction with experimental characterizations, unveil that the interface IEF effect fosters asymmetrical charge distributions, which results in more thermoneutral hydrogen adsorption Gibbs free energy on the electron-deficient Ni side, thus elevating the overall efficiency of both HER and HOR. The discoveries reported herein guidance are provided for further understanding and designing efficient non-precious-metal-based electrocatalysts through the IEF strategy.

Self-Powered Hydrogen Production with Improved Energy Efficiency via Polysulfides Redox.

In the pursuit of efficient solar-driven electrocatalytic water splitting for hydrogen production, the intrinsic challenges posed by the sluggish kinetics of anodic oxygen evolution and intermittent sunlight have prompted the need for innovative energy systems. Here, we introduce an approach by coupling the polysulfides oxidation reaction with the hydrogen evolution reaction for energy-saving H2 production, which could be powered by an aqueous zinc-polysulfides battery to construct a self-powered energy system. This unusual hybrid water electrolyzer achieves 300 mA cm-2 at a low cell voltage of 1.14 V, saving electricity consumption by 100.4% from 5.47 to 2.73 kWh per m3 H2 compared to traditional overall water splitting. Benefiting from the favorable reaction kinetics of polysulfides oxidation/reduction, the aqueous zinc-polysulfides battery exhibits an energy efficiency of approximately 89% at 1.0 mA cm-2. Specially, the zinc-polysulfide battery effectively stores intermittent solar energy as chemical energy during light reaction by solar cells. Under an unassisted light reaction, the batteries could release energy to drive H2 production through a hybrid water electrolyzer for uninterrupted hydrogen production. Therefore, the aim of simultaneously generating H2 and eliminating the restrictions of intermittent sunlight is realized by combining the merits of polysulfides redox, an aqueous metal-polysulfide battery, and solar cells. We believe that this concept and utilization of polysulfides redox will inspire further fascinating attempts for the development of sustainable energy via electrocatalytic reactions.

"Moderate" adjuvant chemotherapy-induced leukopenia is beneficial for survival of patients with early breast cancer: a retrospective study.

BACKGROUND: The association between chemotherapy-induced leukopenia (CIL) and survival for patients with early breast cancer (EBC) is not known. We investigated the relationship between different grades of CIL and survival in patients with EBC receiving adjuvant chemotherapy. METHODS: A total of 442 patients with EBC receiving a regimen containing an anthracycline (A) and taxane (T) were included into our analysis. Survival analyses were undertaken using Kaplan-Meier curves. The P-value was calculated using the log rank test. Subgroup analysis was conducted to investigate the correlation of CIL grade and survival based on the clinicopathological characteristics of patients. Afterwards, univariate and multivariate analyses screened out independent prognostic factors to construct a prognostic model, the robustness of which was verified. RESULTS: Patients with EBC who experienced grade 2-4 ("moderate" and "severe") CIL were associated with longer overall survival (OS) than those with grade 0-1 (mild) CIL (P = 0.021). Compared with patients with mild CIL, OS was longer in patients with severe CIL (P = 0.029). Patients who suffered from moderate CIL tended to have longer OS than those with mild CIL (P = 0.082). Nevertheless, there was no distinguishable difference in OS between moderate- or severe-CIL groups. Subgroup analysis revealed that patients with moderate CIL had longer OS than those with mild CIL among patients who were premenstrual, or with human epidermal growth factor receptor 2-positive (HER2+), > 3 lymph nodes with metastases, a tumor diameter > 5 cm. A prognostic model based on menstrual status, N stage, and CIL grade showed satisfactory robustness. CONCLUSION: The grade of CIL was strongly associated with the prognosis among patients with EBC who received a regimen containing both anthracyclines and taxanes. Patients with a "moderate" CIL grade tended to have better survival outcomes.

High-entropy alloys in electrocatalysis: from fundamentals to applications.

High-entropy alloys (HEAs) comprising five or more elements in near-equiatomic proportions have attracted ever increasing attention for their distinctive properties, such as exceptional strength, corrosion resistance, high hardness, and excellent ductility. The presence of multiple adjacent elements in HEAs provides unique opportunities for novel and adaptable active sites. By carefully selecting the element configuration and composition, these active sites can be optimized for specific purposes. Recently, HEAs have been shown to exhibit remarkable performance in electrocatalytic reactions. Further activity improvement of HEAs is necessary to determine their active sites, investigate the interactions between constituent elements, and understand the reaction mechanisms. Accordingly, a comprehensive review is imperative to capture the advancements in this burgeoning field. In this review, we provide a detailed account of the recent advances in synthetic methods, design principles, and characterization technologies for HEA-based electrocatalysts. Moreover, we discuss the diverse applications of HEAs in electrocatalytic energy conversion reactions, including the hydrogen evolution reaction, hydrogen oxidation reaction, oxygen reduction reaction, oxygen evolution reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, and alcohol oxidation reaction. By comprehensively covering these topics, we aim to elucidate the intricacies of active sites, constituent element interactions, and reaction mechanisms associated with HEAs. Finally, we underscore the imminent challenges and emphasize the significance of both experimental and theoretical perspectives, as well as the potential applications of HEAs in catalysis. We anticipate that this review will encourage further exploration and development of HEAs in electrochemistry-related applications.

An integrated chemical characterization based on FT-NIR, and GC-MS for the comparative metabolite profiling of 3 species of the genus Amomum.

BACKGROUND: The fruits and seeds of genus Amomum are well-known as medicinal plants and edible spices, and are used in countries such as China, India and Vietnam to treat malaria, gastrointestinal disorders and indigestion. The morphological differences between different species are relatively small, and technical characterization and identification techniques are needed. RESULTS: Fourier transform near infrared spectroscopy (FT-NIR) and gas chromatography-mass spectrometry (GC-MS), combined with principal component analysis and two-dimensional correlation analysis were used to characterize the chemical differences of Amomum tsao-ko, Amomum koenigii, and Amomum paratsaoko. The targets and pathways for the treatment of diabetes mellitus in three species were predicted using network pharmacology and screened for the corresponding pharmacodynamic components as potential quality markers. The results of "component-target-pathway" network showed that (+)-Nerolidol, 2-Nonanol, α-Terpineol, α-Pinene, 2-Nonanone had high degree values and may be the main active components. Partial least squares-discriminant analysis (PLS-DA) was further used to select for differential metabolites and was identified as a potential quality marker, 11 in total. PLS-DA and residual network (ResNet) classification models were developed for the identification of 3 species of the genus Amomum, ResNet model is more suitable for the identification study of large volume samples. SIGNIFICANCE: This study characterizes the differences between the three species in a visual way and also provides a reliable technique for their identification, while demonstrating the ability of FT-NIR spectroscopy for fast, easy and accurate species identification. The results of this study lay the foundation for quality evaluation studies of genus Amomum and provide new ideas for the development of new drugs for the treatment of diabetes mellitus.

Response to programmed cell death protein 1 antibody in patients with Epstein-Barr virus-associated intrahepatic cholangiocarcinoma.

AIM: Epstein-Barr virus-associated intrahepatic cholangiocarcinoma (EBVaICC) has a distinct genomic profile and increased CD3+ and CD8+ T cells infiltration. However, the efficacy of immunotherapy in EBVaICC remains largely unknown. This study aimed to assess the efficacy of programmed cell death protein 1 (PD-1) antibody therapy in EBVaICC. METHODS: Patients with metastatic biliary tract cancer (BTC) diagnosed at Sun Yat-sen University Cancer Center from January 2016 to December 2021 were identified. In situ hybridisation was performed to detect EBV. Overall survival (OS) and progression-free survival (PFS) were measured. RESULTS: A total of 698 patients with metastatic BTC were identified, of whom 39 (5.6%) had EBVaICC. Among the 136 patients who were not administered PD-1 antibody, the OS was similar between patients with EBVaICC and EBV-negative ICC (median OS 12.5 versus 9.5 months, respectively; P = 0.692). For the 205 patients who were administered PD-1 antibody, patients with EBVaICC had significantly longer OS than patients with EBV-negative ICC (median OS 24.9 versus 11.9 months, respectively; P = 0.004). Seventeen patients with EBVaICC were administered PD-1 antibody. Eight patients (47%) achieved a partial response, and 17 patients achieved disease control. The median PFS was 17.5 months. CONCLUSIONS: This study identified a clinically actionable subset of patients with EBVaICC with a promising response to the PD-1 antibody.

A new synthesis strategy for nitrogen-doped carbon nanofibers with cobalt oxide nanoparticles as anodic electrode materials for lithium ion batteries.

Nitrogen-doped carbon nanoribbons and nanotubes decorated with Co3O4 nanoparticles were prepared by a metal-catalyzed graphitization-nitridization and oxidization process, using triazole and melamine as a solid nitrogen/carbon co-source, and assessed as anodes of lithium ion batteries (LIBs). These composite anodes display perfect electrochemical performance, indicating their potential for application in LIBs.