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.

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.

Sensing the Small Change of Intermolecular Distance in Supramolecular Assembly by Using the Tunable Emission Wavelength of AIE-Active Luminogens.

The distinct molecular states - single molecule, assembly, and aggregate - of two ionic macromolecules, TPPE-APOSS and TPE-APOSS, are easily distinguishable through their tunable fluorescence emission wavelengths, which reflect variations in intermolecular distances. Both ionic macromolecules contain aggregation-induced emission (AIE) active moieties whose emission wavelengths are directly correlated to their mutual distances in solution: far away from each other as individual molecules, maintaining a tunable and relatively long distance in electrostatic interactions-controlled blackberry-type assemblies (microphase separation), or approaching van der Waals close distance in aggregates (macrophase separation). Furthermore, within the blackberry assemblies, the emission wavelength decreases monotonically with increasing assembly size, indicative of shorter intermolecular distances at nanoscale. The emission changes of TPPE-APOSS blackberry assemblies can even be visually distinguishable by eyes when their sizes and intermolecular distances are tuned. Molecular dynamics simulations further revealed that macromolecules are confined in various conformations by controllable intermolecular distances within the blackberry structure, thereby resulting in fluorescence emission with tunable wavelength.

ITGA7 loss drives the differentiation of adipose-derived mesenchymal stem cells to cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) represent a major cellular component of the tumor (pre-)metastatic niche and play an essential role in omental dissemination of ovarian cancer. The omentum is rich in adipose, and adipose-derived mesenchymal stem cells (ADSCs) have been identified as a source of CAFs. However, the molecular events driving the phenotype shift of ADSCs remain largely unexplored. In this research, we focus on integrins, transmembrane receptors that have been widely involved in cellular plasticity. We found that integrin α7 (ITGA7) was the only member of the integrin family that positively correlated with both overall survival and progression-free survival in ovarian cancer through GEPIA2. The immunohistochemistry signal of ITGA7 was apparent in the tumor stroma, and a lower omental ITGA7 level was associated with metastasis. Primary ADSCs were isolated from the omentum of patients with ovarian cancer and identified by cellular morphology, biomarkers, and multilineage differentiation. The conditional medium of ovarian cancer cells induced ITGA7 expression decrease and phenotypic changes in ADSCs. Downregulation of ITGA7 in primary omental ADSCs led to decrease in stemness properties and emerge of characteristic morphology and biomarkers of CAFs. Moreover, the conditioned medium of ADSCs with ITGA7 depletion exhibited enhanced abilities to improve the migration and invasion of ovarian cancer cells in vitro. Overall, these findings indicate that loss of ITGA7 may induce the differentiation of ADSCs to CAFs that contribute to a tumor-supportive niche.

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.

Long-term exercise preserves pancreatic islet structure and ß-cell mass through attenuation of islet inflammation and fibrosis.

Islet fibrosis is associated with the disruption of islet structure and contributes to ß-cell dysfunction, playing an essential role in the pathogenesis of type 2 diabetes. Physical exercise has been shown to attenuate fibrosis in various organs; however, the effect of exercise on islet fibrosis has not been defined. Male Sprague-Dawley rats were divided into four groups: normal diet sedentary [N-Sed], normal diet + exercise [N-Ex], high-fat diet sedentary [H-Sed], and high-fat diet + exercise [H-Ex]. After 60 weeks of exercise, 4452 islets from Masson-stained slides were analyzed. Exercise led to a 68% and 45% reduction in islet fibrosis in the normal and high-fat diet groups and was correlated with a lower serum blood glucose. Fibrotic islets were characterized by irregular shapes and substantial loss of ß-cell mass, which were significantly reduced in the exercise groups. Remarkably, the islets from exercised rats at week 60 were morphologically comparable to those of sedentary rats at 26 weeks. In addition, the protein and RNA levels of collagen and fibronectin, and the protein levels of hydroxyproline in the islets were also attenuated by exercise. This was accompanied by a significant reduction in inflammatory markers in the circulation Interleukin-1 beta (IL-1ß)] and pancreas [IL-1ß, Tumor Necrosis Factor-alpha, Transforming Growth Factor-ß, and Phosphorylated Nuclear Factor Kappa-B p65 subunit], lower macrophage infiltration, and stellate cell activation in the islets of exercised rats. In conclusion, we have demonstrated that long-term exercise preserves pancreatic islet structure and ß-cell mass through anti-inflammatory and anti-fibrotic actions, suggesting additional rationales for the success of exercise training in the prevention and treatment of type 2 diabetes that should be further explored.

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.

Chinese Anesthesiology Milestones in Resident Evaluation: Reliability, Validity, and Correlation with Objective Examination Scores: a Cross-sectional Study.

BACKGROUND: Evaluating competency acquisition during residency training is crucial. The Anesthesiology Milestones have been implemented in the United States. The China Consortium of Elite Teaching Hospitals for Residency Education has also developed the Chinese Resident Core Competency Milestone Evaluation System. Despite this, Milestones tailored for anesthesiology have yet to be implemented in China. To address this gap, we have developed Chinese Anesthesiology Milestones. This study aims to assess the reliability and validity of the Chinese Anesthesiology Milestones and their correlation with objective examinations. METHODS: In this single-center cross-sectional study, we included anesthesia residents enrolled in the standardized residency training program at our hospital during the academic year 2021 to 2022. The Chinese Anesthesiology Milestones were developed based on the American version of Anesthesiology Milestones 2.0 and the Chinese Resident Core Competency Milestone Evaluation System using the Delphi method. The Delphi panel comprised a diverse group, including education administrators, faculty from teaching hospitals, and anesthesia residents. Five attending anesthesiologists independently assessed the levels achieved by each anesthesia resident based on the Chinese Anesthesiology Milestones. Subsequently, they collaboratively discussed the ratings for each resident until a consensus was reached. The interrater reliability, internal consistency, and construct validity were assessed using Kendall's coefficient, Cronbach's α coefficient/ composite reliability, and average variance extracted, respectively. Higher values indicated better reliability or validity. The correlation between Milestone ratings and objective examination scores, including written examinations and Objective Structured Clinical Examinations, were analyzed using Pearson correlation. RESULTS: The Chinese Anesthesiology Milestones encompassed 6 competencies, including professionalism, medical knowledge and technical skills, patient care, interpersonal and communication skills, teaching ability, and life-long learning. Milestone evaluation data were available and analyzed from 66 residents. The Kendall's coefficient of concordance among raters ranged from 0.799 (95% confidence interval [CI], 0.793-0.918) to 0.942 (95% CI, 0.934-0.982). The average variance extracted, composite reliability, and Cronbach's α coefficient ranged from 0.782 to 0.920, 0.935 to 0.980, and 0.916 to 0.978, respectively. Correlations between objective examination scores and related Milestone subcompetencies were as follows: written examinations: r = 0.52 (95% CI, 0.22-0.71), technical skills stations: r = 0.51 (95% CI, 0.21-0.71), the oral test station: r = 0.66 (95% CI, 0.45-0.79), and the standardized patient station: r = 0.61 (95% CI, 0.36-0.76). CONCLUSIONS: The Chinese Anesthesiology Milestones demonstrated satisfactory interrater reliability, internal consistency, construct validity, and correlation with objective examination scores within our hospital.

Antepartum risk factors and outcomes of massive transfusion for elective cesarean section: a nationwide retrospective cohort study.

BACKGROUND: Postpartum hemorrhage is one of the leading causes of maternal mortality and morbidity. The etiology of postpartum hemorrhage exhibits variations in relation to the mode of birth; consequently, risk factors for massive transfusion in elective cesarean section might diverge from those encountered in vaginal birth or emergency cesarean section. The main purpose of this study was to investigate antepartum risk factors of massive transfusion for elective cesarean section. METHODS: We conducted a retrospective cohort study based on data from a nationwide system that collected inpatient medical records from tertiary hospitals in mainland China. We included women who had undergone elective cesarean section from January 2013 to August 2018. Primary outcome was massive transfusion defined as transfusion of more than eight units of red blood cells on the day of childbirth. Candidate risk factors were identified by the 10th revision of International Classification of Diseases Codes of admission diagnoses. The relationship between each factor and massive transfusion was assessed using multivariable logistic regression. RESULTS: A total of 294,695 women were included and 572 of them received massive transfusion (incidence: 194 per 100,000 elective cesarean sections). Maternal age [adjusted odds ratio (aOR) 1.22; 95% confidence interval (CI) 1.10-1.48], anemia (aOR 1.66; 95% CI 1.34-2.05), thrombocytopenia (aOR 3.54; 95% CI 2.39-5.05), coagulopathy (aOR 25.92; 95% CI 8.59-69.50), hypoalbuminemia (aOR 2.97; 95% CI 1.86-4.53), hepatic dysfunction (aOR 1.65; 95% CI 1.04-2.47), uterine scar (aOR 1.39; 95% CI 1.15-1.67), multiple pregnancy (aOR 2.84; 95% CI 1.74-4.38), polyhydramnios (aOR 2.52; 95% CI 1.19-4.68) and placenta previa (aOR 25.03; 95% CI 21.04-29.77) were associated with massive blood transfusion for elective cesarean section. Among the women receiving massive blood transfusion, 7 (1.2%) died during hospitalization, 126 (22.0%) needed hysterectomy, 25 (4.4%) uterine packing and 57 (10.0%) uterine artery ligation. CONCLUSIONS: Ten risk factors of massive transfusion were identified in women undergoing elective cesarean section. Our findings may facilitate blood products preparation and provide opportunities for applying prophylactic strategies prior to cesarean section for women at high risk of massive transfusion.

Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy.

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.

A novel correction method for modelling parameter-driven autocorrelated time series with count outcome.

BACKGROUND: Count time series (e.g., daily deaths) are a very common type of data in environmental health research. The series is generally autocorrelated, while the widely used generalized linear model is based on the assumption of independent outcomes. None of the existing methods for modelling parameter-driven count time series can obtain consistent and reliable standard error of parameter estimates, causing potential inflation of type I error rate. METHODS: We proposed a new maximum significant ρ correction (MSRC) method that utilizes information of significant autocorrelation coefficient ρ estimate within 5 orders by moment estimation. A Monte Carlo simulation was conducted to evaluate and compare the finite sample performance of the MSRC and classical unbiased correction (UB-corrected) method. We demonstrated a real-data analysis for assessing the effect of drunk driving regulations on the incidence of road traffic injuries (RTIs) using MSRC in Shenzhen, China. Moreover, there is no previous paper assessing the time-varying intervention effect and considering autocorrelation based on daily data of RTIs. RESULTS: Both methods had a small bias in the regression coefficients. The autocorrelation coefficient estimated by UB-corrected is slightly underestimated at high autocorrelation (≥ 0.6), leading to the inflation of the type I error rate. The new method well controlled the type I error rate when the sample size reached 340. Moreover, the power of MSRC increased with increasing sample size and effect size and decreasing nuisance parameters, and it approached UB-corrected when ρ was small (≤ 0.4), but became more reliable as autocorrelation increased further. The daily data of RTIs exhibited significant autocorrelation after controlling for potential confounding, and therefore the MSRC was preferable to the UB-corrected. The intervention contributed to a decrease in the incidence of RTIs by 8.34% (95% CI, -5.69-20.51%), 45.07% (95% CI, 25.86-59.30%) and 42.94% (95% CI, 9.56-64.00%) at 1, 3 and 5 years after the implementation of the intervention, respectively. CONCLUSIONS: The proposed MSRC method provides a reliable and consistent approach for modelling parameter-driven time series with autocorrelated count data. It offers improved estimation compared to existing methods. The strict drunk driving regulations can reduce the risk of RTIs.

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.

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.

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.

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.

Human papillomavirus vaccination and contributing factors of vaccination intention among adolescents and young adults in China from a socio-ecological perspective: A cross-sectional study.

OBJECTIVES: Adolescents and young adults are the main target population for human papillomavirus (HPV). The study aimed to investigate school students' HPV vaccination intentions and explore the contributing factors from a socio-ecological perspective. DESIGN: A questionnaire survey was conducted in three secondary schools and three colleges in China. SAMPLE: A total of 1756 students aged 14-22 years participated in this study. Among the 1756 participants, 182 students have received the HPV vaccine. For the remaining 1574 students, we analyzed their HPV vaccination intentions and the influencing factors. MEASUREMENTS: Survey items for sociodemographics, knowledge and awareness of HPV, sexual intercourse and sexual knowledge, subjective socioeconomic status, self-efficacy, eHealth literacy, perceived social support from family, and the availability of HPV vaccine information were measured. RESULTS: Only 182 (10.4%) had received the HPV vaccine among the 1756 participants. Among the remaining 1574 students, the majority of the students (1403, 89.1%) were willing to receive the HPV vaccine. Binary logistic regression analysis showed that students who were female, had lower self-efficacy, scored higher on sexual knowledge, believed vaccination preventing related diseases, worried about side effects after vaccination, thought oneself at risk of contracting HPV, had higher family support, knew the availability of the HPV vaccine in Mainland China from healthcare institutions, and with family residence in rural areas were more willing to receive the HPV vaccine. CONCLUSIONS: Students had high HPV vaccination intentions while had low vaccination rate. Intrapersonal, interpersonal and institutional or community factors predicted HPV vaccination intention. Public health nurses in communities and schools could target the modifiable factors to promote students' HPV vaccine uptake.

[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.

Association between Storage Time of Transfused Red Blood Cells and Infection after Clean-contaminated Surgery: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to investigate the association between storage time of transfused red blood cells and risks of infections after clean-contaminated surgery. SUMMARY BACKGROUND DATA: Storage lesions of red blood cells can aggravate transfusion-related immunomodulation. Very few randomized controlled trials have investigated the impacts of storage time on postoperative outcomes in non-cardiac patients. METHODS: We included adult patients who had undergone clean-contaminated surgery from 2014 to 2018 and received allogeneic red blood cell transfusion. In transfusion episode-level analysis, the exposure was the storage time of each transfusion episode. In patient-level analysis, the exposures were the mean, weighted mean, maximum storage time, and Scalar Age of Blood Index of red blood cells transfused into each patient. The primary outcome was infections that developed after transfusions within postoperative Day 30. RESULTS: The 4046 included patients received 11604 transfusion episodes. Of these, 1025 (25.3%) patients developed postoperative infections. An increased storage time of transfused red blood cells was not associated with increased odds of postoperative infections in either transfusion episode-level analysis [odds ratio (OR) 1.03 per five days, 95% confidence interval (CI) 0.95 to 1.11] or patient-level analysis (mean: OR 1.02, 95% CI 0.95 to 1.10; weighted mean: OR 1.02, 95% CI 0.95 to 1.10; maximum: OR 1.06, 95% CI 0.98 to 1.14; Scalar Age of Blood Index: OR 0.99, 95% CI 0.96 to 1.03), after adjusting 17 confounders. CONCLUSIONS: Prolonged storage time of transfused red blood cells was not associated with increased risks of infections after clean-contaminated surgery.

Temporal trends and geographic variations in perioperative red blood cell transfusion in major surgical procedures from 2013 to 2018 in China.

BACKGROUND AND OBJECTIVES: Transfusion-related guidelines promote restrictive blood transfusion. However, whether these guidelines have been successfully translated into clinical practice in China is unknown. This study aimed to provide updated information about the temporal trends in the prevalence of perioperative red blood cell (RBC) transfusion in China. MATERIALS AND METHODS: We analysed data from the Hospital Quality Monitoring System database (2013-2018) to investigate the prevalence of perioperative RBC transfusion in patients undergoing craniotomy for cerebral aneurysms or arteriovenous malformations, sternotomy for mitral valve replacement, open thoracotomy lobectomy, open gastrectomy and hip arthroplasty. Mixed-effects logistic regression models quantified the likelihood of RBC transfusions. RESULTS: The study included 438,183 patients, with 44,697 (10.20%) receiving perioperative RBC transfusions. Introducing transfusion-related guidelines in China markedly decreased the prevalence of RBC transfusion among patients who underwent major surgical procedures in the following years. The prevalence of RBC transfusion for hip arthroplasty was 17.34% in 2013 and 7.03% in 2018. After adjusting for patient risk factors, the odds ratio of RBC transfusion for hip arthroplasty was significantly lower in 2018 (0.74, 95% confidence intervals [CI] 0.53-1.02) than in 2013 (1.84, 95% CI 1.37-2.48). CONCLUSION: The prevalence of perioperative RBC transfusion decreased from 2013 to 2018 in China, supporting the potential beneficial effects of transfusion-related guidelines. Considering the geographic variations in RBC transfusion, reducing heterogeneity may impact public health by improving surgical outcomes.

Roles of microRNAs and exosomes in Helicobacter pylori associated gastric cancer.

Helicobacter pylori (H. pylori) is a common pathogen that infects more than half of the world's population. Its infection can not only lead to a variety of gastrointestinal diseases, such as chronic gastritis and gastric cancer (GC) but also be associated with many extra-gastrointestinal diseases. Exosomes, as a new intercellular information transmission medium, can carry biological signal molecules such as microRNAs (miRNAs) to regulate a variety of cellular physiological activities and are involved in multiple cancer processes. In this article, we provide a systematic review on the role of exosomal miRNAs in H. pylori-associated GC.