Blood-derived factors to brain communication in brain diseases.

Brain diseases, mainly including acute brain injuries, neurodegenerative diseases, and mental disorders, have posed a significant threat to human health worldwide. Due to the limited regenerative capability and the existence of the blood-brain barrier, the brain was previously thought to be separated from the rest of the body. Currently, various cross-talks between the central nervous system (CNS) and peripheral organs have been widely described, including the brain-gut axis, the brain-liver axis, the brain-skeletal muscle axis, and the brain-bone axis. Moreover, several lines of evidence indicate that leveraging systemic biology intervention approaches, including but not limited to lifestyle interventions, exercise, diet, blood administration, and peripheral immune responses, have demonstrated a significant influence on the progress and prognosis of brain diseases. The advancement of innovative proteomic and transcriptomic technologies has enriched our understanding of the nuanced interplay between peripheral organs and brain diseases. An array of novel or previously underappreciated blood-derived factors have been identified to play pivotal roles in mediating these communications. In this review, we provide a comprehensive summary of blood-to-brain communication following brain diseases. Special attention is given to the instrumental role of blood-derived signals, positing them as significant contributors to the complex process of brain diseases. The insights presented here aim to bridge the current knowledge gaps and inspire novel therapeutic strategies for brain diseases.

Targeted Delivery of 2D Composite Minerals for Biofilm Removal.

Microbiologically influenced corrosion (MIC) poses considerable challenges in various industries, prompting the exploration of advanced materials to mitigate microbial threats. This study successfully synthesized nanoscale vermiculite (VMT) from natural seawater and utilized it as a foundation to integrate magnetic nanoparticles (Fe3O4) and chlorhexidine acetate (CA) for inhibiting MIC. A comprehensive investigation encompassing the synthesis, characterization, and application of these VMT/Fe3O4/CA composites was conducted to evaluate their antimicrobial effectiveness against Escherichia coli, Staphylococcus aureus, and sulfate-reducing bacteria (SRB), demonstrating an efficacy exceeding 99.5%. Moreover, the composite material demonstrated the capability to align with a magnetic field, enabling precise drug targeting and release, thereby facilitating biofilm removal. This research makes a significant contribution to the advancement of intelligent, efficient, and eco-friendly corrosion protection solutions.

Light-Triggered Plasmonic DNAzyme Walker Enables Precise Subcellular Molecular Imaging with Reduced Off-Mitochondria Signal Leakage.

The development of highly sensitive and precise imaging techniques capable of visualizing crucial molecules at the subcellular level is essential for elucidating mitochondrial functions and uncovering novel mechanisms in biological processes. However, traditional molecular imaging strategies are still limited by off-mitochondria signal leakage because of the "always-active" sensing mode. To address this limitation, we have developed a light-triggered activation sequence activated plasmonic DNAzyme walker (PDW) for accurate subcellular molecular imaging by the combination of an organelle localized strategy, upconversion nanotechnology, and a plasmon enhanced fluorescence (PEF) technique. Exploiting the advantage of light activation enables precise control over when and where to activate the probe's sensing function, effectively reducing off-mitochondria signal leakage as validated by the dynamic monitoring of changes in off-mitochondria signals during the mitochondrial entry process. Furthermore, by leveraging the PEF capability of triangular gold nanoprisms (Au NPRs), the fluorescence intensity can be enhanced by approximately 11.9 times, ensuring highly sensitive and accurate subcellular molecular imaging.

Remote ischemic conditioning slows blood-retinal barrier damage in type 1 diabetic rats.

Diabetic retinopathy (DR) is one of the major complications of diabetes and can cause severe visual impairment. Blood-retina barrier (BRB) destruction resulted from chronic hyperglycemia underlines its major pathological process. However, current treatments have limited efficacy and may even cause serious complications. Remote ischemic conditioning (RIC), through repeated transient mechanical occlusion of limb blood vessels, has been confirmed to promote blood-brain barrier integrity after stroke, but its role in BRB disruption has not been elucidated. This study aimed to investigate the protective effects of RIC on the BRB in diabetic rats and its potential mechanisms. 48 Sprague-Dawley rats were randomly assigned to the Sham group, Sham + RIC group, diabetes mellitus (DM) group and DM+RIC group. The diabetic model was successfully induced by intraperitoneal injection of streptozotocin (STZ). RIC treatment was administered daily and lasted for 9 weeks. In functional analysis, RIC improved the retinal function based on electroretinogram data and reduced the leakage of BRB in diabetic rats. In proteomic analysis, tight junction pathway was enriched after RIC treatment, in which Patj gene was significantly increased. We also found that RIC increased mRNA levels of Patj, claudin-1 and zonula occludens (ZO)-1, protein expression of claudin-1 when compared with diabetic models. In conclusion, RIC slowed BRB damage in diabetic rats which may be related to the preservation of tight junction proteins. RIC may be a promising protective strategy for the treatment of DR.

Intervention of inflammation associated with ankylosing spondylitis by triptolide promotes histone H3 Iys-27 trimethylation.

Objective: This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS).Methods: Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway.Results: We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt (p < 0.05), JAK2 and STAT3 (JAK2: p < 0.05; STAT3: p < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene.Conclusion: Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.

Complex microplastics significantly influence the assembly process of lake bacterial communities.

Environmental microplastics (MPs) vary in abundance, shape, size, color, and polymer type in freshwater ecosystems, yet their impact on bacterial community assembly in natural lakes is unclear. Here, we examined MPs and bacterial compositions in water and sediments of Taihu Lake, China, to reveal the influence of complex MPs on the bacterial community assembly. The results showed that the complexity index of MPs significantly influenced the turnover and nestedness components of bacterial communities. In the colder season, MP complexity was significantly correlated with the turnover componentin sediments (R2 = 0.19, P < 0.0001), with turnover increasing as MP complexity increased. Conversely, under warmer season, MP complexity was significantly correlated with turnover and nestedness components. Additionally, the interaction effect of environmental and MP factors affected almost all components of beta diversity, particularly in cold water and sediment, with impacts on nestedness of 0.17 and 0.12, respectively, and should thus not be ignored. Our findings indicate for the first time that complex MPs significantly influence the assembly of bacterial communities in lake systems. The impact varies across seasons and future warming may exacerbate this effect, rendering it more uncertain and complex.

Integration of interpretable machine learning and environmental magnetism elucidates reduction mechanism of bioavailable potentially toxic elements in lakes after monsoon.

Little information is available on the influence of substantial precipitation and particulate matter entering during the monsoon process on the release of potentially toxic elements (PTEs) into lake sediments. Sediments from a typical subtropical lake across three periods, pre-monsoon, monsoon, and post-monsoon, were collected to determine the chemical forms of 12 PTEs (As, Cd, Co, Cr, Cu, Fe, Hg, Pb, Mn, Ni, Sb, and Zn), magnetic properties, and physicochemical indicators. Feature importance, Shapley additive explanations, and partial dependence plots were used to explore the factors influencing bioavailable PTEs. The proportion of bioavailable forms of PTEs decreased from 3.85 % (Cd) to 87.84 % (Hg) after the monsoon. Gradient extreme boosting demonstrated robust fitting accuracy for the prediction of the bioavailable forms of the 12 PTEs (R2 > 0.84). Shapley additive explanations identified that the bioavailable forms were influenced by the total PTE concentrations, wind, shortwave radiation, and particle inputs (25.1 %-88.5 % for total importance), either individually or in combination. The partial dependence plots highlighted the influence thresholds of background values and anthropogenic factors on the bioavailable forms of PTEs. Changes in environmental properties could indicate the process of external sediment influx into lakes. The optimized model combined with magnetic parameters showed strong performance in other cases (coefficient of determination>0.58), confirming the ubiquitous decrease in bioavailable forms of PTEs in sediments across subtropical lakes after monsoons.

Fiddler crabs (Tubuca arcuata) as bioindicators of microplastic pollution in mangrove sediments.

In recent years, microplastics (MPs) have been widely found in the environment and pose potential risks to ecosystems, which attracted people's attention. Using bioindicators has been a great approach to understanding the pollution levels, bioavailability, and ecological risks of pollutants. However, only few studies have investigated MPs in mangrove ecosystems, with few bioindicators of MPs. Herein, the distribution of MPs in mangrove sediments and fiddler crabs (Tubuca arcuata) in mangroves was investigated. Results showed that the abundance values of MPs are 1160‒12,120 items/kg and 11-100 items/ind. in mangrove sediments and fiddler crabs, respectively. The dominant shape of MPs detected in mangrove sediments and fiddler crabs was fragments with sizes of 20‒1000 µm, larger MPs of 50-1000 µm were found in abundance. Polypropylene (PP), which is one of the most commonly used plastic materials, was the main polymer type. The distribution of MPs in fiddler crabs closely resembled that in surface mangrove sediments with a strong linear correlation (R2 > 0.8 and p < 0.05) between their abundance. Therefore, the MP contamination level in mangrove sediments can be determined by studying MP pollution in fiddler crabs. Moreover, the results of the target group index (TGI) indicated that fiddler crabs prefer feeding specific MPs in mangrove sediments. Our findings demonstrate the suitability of fiddler crabs as bioindicators for assessing MP pollution in mangrove sediments.

A ß-1,3/1,6-glucan enhances anti-tumor effects of PD1 antibody by reprogramming tumor microenvironment.

Checkpoint blockades have emerged as a frontline approach in cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of pattern recognition receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication. Previously, a ß-1,3/1,6-glucan with high purity from Durvillaea antarctica (BG136) was reported by our group to exhibit pan-antitumor effects. In the current study, we systemically studied the antitumor activity of BG136 in combination with anti-PD1 antibody in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggested that BG136 enhanced the antitumor immunity of anti-PD1 antibody by reprogramming the tumor microenvironment to become more proinflammatory. In addition, an increase in innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, and a decrease in ascorbate and aldarate metabolism were also found. These findings provide mechanistic insights that support the potent antitumor efficacy of BG136 when combined with immune checkpoint inhibitor antibodies.

A Two-step Intermolecular Interaction of Molecular Macroions with Multivalent Counterions.

Macroion-counterion interaction is essential for regulating the solution behaviors of hydrophilic macroions, as simple models for polyelectrolytes. Here, we explore the interaction between uranyl peroxide molecular cluster Li68K12(OH)20[UO2(O2)OH]60 (U60) and multivalent counterions. Different from interaction with monovalent counterions that shows a simple one-step process, isothermal titration calorimetry, combined with light/X-ray scattering measurements and electron microscopy, confirm a two-step process for their interaction with multivalent counterions: an ion-pairing between U60 and the counterion with partial breakage of hydration shells followed by strong U60-U60 attraction, leading to the formation of large nanosheets with severe breakage and reconstruction of hydration shells. The detailed studies on macroion-counterion interaction can be nicely correlated to the microscopic (self-assembly) and macroscopic (gelation or phase separation) phase transitions in the dilute U60 aqueous solutions induced by multivalent counterions.

Coacervate Formation in Dilute Aqueous Solutions of Inorganic Molecular Clusters with Simple Divalent Countercations.

We report a complex coacervate formed by a 2.5 nm-diameter, rigid uranyl peroxide molecular cluster (Li68K12(OH)20)[UO2(O2)OH]60, U6060-) and SrCl2 salt in dilute aqueous solutions, including its location in the phase diagram, composition, rheological features, and critical conditions for phase transitions. In this coacervate, the Sr2+ cations are a major building component, and the coacervate phase covers a substantial region of the phase diagram. This coacervate demonstrates features that differ from traditional coacervates formed by oppositely charged long-chain polyelectrolytes, especially in its formation mechanism, dehydration, enhancement of mechanical strength with increasing ionic strength, and the change of salt partition preference into the coacervate and supernatant phases with ionic strength.

Can the postload-fasting glucose gap be used to determine risk of developing diabetes in chinese adults: A prospective cohort study.

OBJECTIVE: To evaluate the relationship between fasting plasma glucose (FPG) and 2-hour postload plasma glucose (2hPG) measured during an oral glucose tolerance test, and the risk of developing diabetes in Chinese adults. METHODS: We followed 3,094 participants without diabetes, categorizing them based on their oral glucose tolerance test (OGTT) results into low post load (2hPG ≤ FPG) and high post load (2hPG > FPG) at baseline. We monitored the incidence of diabetes, incidence of prediabetes, disease progression from prediabetes to diabetes and disease reversal from prediabetes to normal glucose tolerance (NGT) over an average of 3.2 years of follow-up. After the Schoenfeld residual test, Cox's time-varying covariate (Cox-TVC) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) to compare the different clinical events between low and high post load groups. RESULTS: In the cohort study, of the 3,094 participants, 702 (22.7 %) had low post load (2hPG ≤ FPG, mean postload-fasting gap: -0.8 ± 0.7 mmol/L) and 2,392 (77.3 %) had high post load (2hPG > FPG, mean postload-fasting gap: 1.8 ± 1.2 mmol/L). Over 3.2 ± 0.2 years of follow-up, 282 (9.1 %) developed diabetes. In the low post load group, the incidence rates per 1,000 person-years were: diabetes was 7.9, prediabetes was 70.0, disease progression from prediabetes to diabetes was 23.4 and disease reversal to NGT was 327.2. For the high post load group, incidence rates for diabetes was 13.9, prediabetes was 124.3, disease progression was 59.5 and disease reversal was 238.6 per 1,000 person-years. Participants with high post load showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal was lower. CONCLUSION: The risk of developing prediabetes/diabetes after 3.2 years of follow-up was higher in the participants with high post load. It suggested that postload-fasting gap may be a simple tool to predict the risk of developing prediabetes, diabetes or reversal to NGT.

Mechanistic characterization of dissolved inorganic phosphorus in water during the red tide.

The eutrophication of water, such as excessive nitrogen and phosphorus, are closely associated with the outbreak of red tide. However, the response of dissolved inorganic phosphorus (DIP) to red tide remained unclear in water. In this study, three species of diatoms capable of causing red tides were cultured in simulated seawater with different concentrations of DIP. The changes of biomass, chlorophyll a concentration and the carbon stable isotope composition of microalgae, the DIP concentration and pH of the culture medium were compared among the experimental groups. In addition, correlation verification was used to test the correlation between the change of DIP concentration and other indicators. The results showed that in the experimental period, the DIP concentration of each experimental group decreased significantly first, and the concentration dropped to less than 40% of the initial level. After that, the pH of the medium, the biomass, chlorophyll a concentration and carbon stable isotope composition of the microalgae showed varying degrees of increase, and then stabilized or decreased. These also marked the outbreak of red tide. Moreover, the correlation test showed that there was a correlation between them and the change of DIP concentration. Therefore, by exploring the relationship between the change of DIP concentration in water and the occurrence of red tide, this study provides a possible direction for the current prediction of red tide, and provides a basis for further investigation of the occurrence mechanism of red tide.

Clinical performance of the ASAS health index in chinese patients with ankylosing spondylitis and its influencing factors.

OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. CONCLUSION: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.

Thermal facial image analyses reveal quantitative hallmarks of aging and metabolic diseases.

Although human core body temperature is known to decrease with age, the age dependency of facial temperature and its potential to indicate aging rate or aging-related diseases remains uncertain. Here, we collected thermal facial images of 2,811 Han Chinese individuals 20-90 years old, developed the ThermoFace method to automatically process and analyze images, and then generated thermal age and disease prediction models. The ThermoFace deep learning model for thermal facial age has a mean absolute deviation of about 5 years in cross-validation and 5.18 years in an independent cohort. The difference between predicted and chronological age is highly associated with metabolic parameters, sleep time, and gene expression pathways like DNA repair, lipolysis, and ATPase in the blood transcriptome, and it is modifiable by exercise. Consistently, ThermoFace disease predictors forecast metabolic diseases like fatty liver with high accuracy (AUC > 0.80), with predicted disease probability correlated with metabolic parameters.

Unlocking the Potential of CO2 Capture: A Synergistic Hybridization Strategy for Polymeric Hydrogels with Tunable Physicochemical Properties.

Unlocking CO2 capture potential remains a complex and challenging endeavor. Here, a blueprint is crafted for optimizing materials through CO2 capture and developing a synergistic hybridization strategy that involves synthesizing CO2-responsive hydrogels by integrating polymeric networks interpenetrated with polyethyleneimine (PEI) chains and inorganic CaCl2. Diverging from conventional CO2 absorbents, which typically serve a singular function in CO2 capture, these hybrid PEAC hydrogels additionally harness its presence to tune their optical and mechanical properties once interacting with CO2. Such synergistic functions entail two significant steps: (i) rapid CO2-fixing through PEI chains to generate abundant carbamic acid and carbamate species and (ii) mineralization via CaCl2 to induce the formation of CaCO3 micro-crystals within the hydrogel matrix. Due to the reversible bonding, the PEAC hydrogels enable the decoupling of CO2 through an acid fumigation treatment or a heating process, achieving dynamic CO2 capture-release cycles up to 8 times. Furthermore, the polyethyleneimine-acrylamide-calcium chloride (PEAC) hydrogel exhibits varying antibacterial attributes and high interfacial adhesive strength, which can be modulated by fine-tuning the compositions of PEI and CaCl2. This versatility underscores the promising potential of PEAC hydrogels, which not only unlocks CO2 capture capabilities but also offers opportunities in diverse biological and biomedical applications.

The fluoride exporter (CsFEX) regulates fluoride uptake/accumulation in Camellia sinensis under different pH.

Fluoride (F) can be absorbed from the environment and hyperaccumulate in leaves of Camellia sinensis without exhibiting any toxic symptoms. Fluoride exporter in C. sinensis (CsFEX) could transport F to extracellular environment to alleviate F accumulation and F toxicity, but its functional mechanism remains unclear. Here, combining with pH condition of C. sinensis growth, the characteristics of CsFEX and mechanism of F detoxification were further explored. The results showed that F accumulation was influenced by various pH, and pH 4.5 and 6.5 had a greater impact on the F accumulation of C. sinensis. Through Non-invasive Micro-test Technology (NMT) detection, it was found that F uptake/accumulation of C. sinensis and Arabidopsis thaliana might be affected by pH through changing the transmembrane electrochemical proton gradient of roots. Furthermore, diverse expression patterns of CsFEX were induced by F treatment under different pH, which was basically up-regulated in response to high F accumulation, indicating that CsFEX was likely to participate in the process of F accumulation in C. sinensis and this process might be regulated by pH. Additionally, CsFEX functioned in the mitigation of F sensitivity and accumulation strengthened by lower pH in Escherichia coli and A. thaliana. Moreover, the changes of H+ flux and potential gradient caused by F were relieved as well in transgenic lines, also suggesting that CsFEX might play an important role in the process of F accumulation. Above all, F uptake/accumulation were alleviated in E. coli and A. thaliana by CsFEX through exporting F-, especially at lower pH, implying that CsFEX might regulate F accumulation in C. sinensis.

Efficacy of bougie first approach for endotracheal intubation with video laryngoscopy during continuous chest compression: a randomized crossover manikin trial.

BACKGROUND: Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression. METHODS: This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute. RESULTS: A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants. CONCLUSIONS: The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings. TRIAL REGISTRATION: Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.

Differences between resident self-assessments and faculty- assessments on Anesthesiology Milestones and associated factors: a cross-sectional study.

BACKGROUND: Accurate self-assessment is crucial for the professional development of physicians. There has been sparse data on the accuracy of self-assessments on Anesthesiology Milestones. The aim of this study was to investigate the differences between resident self-assessments and faculty-assessments on Anesthesiology Milestones and the associated factors. METHODS: This was a cross-sectional study conducted in a general tertiary university-affiliated hospital. We included anesthesia residents who were enrolled in the standardized residency training program in postgraduate year two and three at the time of the Milestone evaluation. We requested evaluations of competencies from both the Clinical Competency Committee faculty and the anesthesia residents themselves, utilizing the Chinese version of Anesthesiology Milestones in January 2023 and January 2024. The primary outcome was the differences between self- and faculty-assessments, calculated by subtracting the faculty-rated score from the self-rated score on each subcompetency. RESULTS: A total of 46 and 42 residents were evaluated in year 2023 and 2024, respectively. The self-rated sum score was significantly higher than that rated by faculty [mean (standardized deviation): 120.39 (32.41) vs. 114.44 (23.71), P = 0.008 in paired t test] with an intraclass correlation coefficient of 0.55 [95% confidence interval (CI): 0.31 to 0.70]. The Bland-Altman plots revealed significant overestimation in patient care (bias 0.32, 95% CI: 0.05 to 0.60), practice-based learning and improvement (bias 0.45, 95% CI: 0.07 to 0.84), and professionalism (bias 0.37, 95% CI: 0.02 to 0.72). Ratings from residents with master's degrees (mean difference: -1.06, 95% CI: -1.80 to -0.32, P = 0.005) and doctorate degrees (mean difference: -1.14, 95% CI: -1.91 to -0.38, P = 0.003) were closer to the faculty-assessments than residents with bachelor's degrees. Compared with patient care, the differences between self- and faculty- rated scores were smaller in medical knowledge (mean difference: -0.18, 95% CI: -0.35 to -0.02, P = 0.031) and interpersonal and communication skills (mean difference: -0.41, 95% CI: -0.64 to -0.19, P < 0.001) in the generalized estimating equation logistic regression model. CONCLUSIONS: This study revealed that residents tended to overestimate themselves, emphasizing the need to improve the accuracy of Milestones self-assessment. The differences between self- and faculty-assessments were associated with residents' degrees and domains of competency.

[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.