A functional dual responsive CMC/OHA/SA/TOB hydrogel as wound dressing to enhance wound healing.

Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague-Dawley (SD) rat was employed to investigate the hydrogel's wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel's proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Evaluating vitamin D status in Chinese pre-school children using dried blood spots coupled with liquid chromatograph coupled with mass spectrometer.

AIM: Vitamin D is an essential micronutrient for multiple physiological processes, and its deficiency remains a world-wide public health problem that cannot be ignored. Dried blood spot (DBS) is a convenient tool in large-scale epidemiological studies, but its application in evaluating vitamin D status in Chinese population is still scarce. Herein, we aimed to determine the vitamin D status in Chinese pre-school children using DBS coupled with LC-MS/MS method. METHODS: We first developed a sensitive and reliable method for the determination of 25-hydroxyvitamin D (25(OH)D) in DBS samples using an ultra-high-performance liquid chromatograph coupled with triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Next, we conducted a pilot study to compare the 25(OH)D concentration in DBS and serum samples. Finally, the assay method was used to evaluate vitamin D status in Chinese pre-school children. RESULTS: The present method was validated to be reliable and robust for the determination of 25(OH)D in DBS samples. Comparable consistency was observed between the 25(OH)D concentration in DBS and serum samples. A total of 3826 DBS samples collected from children aged 1-7 years were determined. The median concentration of 25(OH)D was 19.57 ng/mL (interquartile range 14.73-24.36 ng/mL), and decreased from 1 to 7 years of age. In addition, 13.51% of male children and 15.12% female children are found to be deficient in 25(OH)D. CONCLUSIONS: DBS coupled with LC-MS/MS is a feasible strategy to evaluate vitamin D status in epidemiological studies. And vitamin D deficiency remains a common health problem in Chinese pre-school children.

Self-Regulated Learning and Learning Outcomes in Undergraduate and Graduate Medical Education: A Meta-Analysis.

Self-regulated learning (SRL) plays a pivotal role in medical education. There is a pressing need for a meta-analytical review to comprehensively evaluate the effect sizes of SRL strategies across diverse learning outcomes and levels of medical trainees. A meta-analysis was executed by searching five databases and resulted in 61 studies that met our inclusion criteria. A three-level meta-analysis was performed to examine the association between SRL strategies and various levels of learning outcomes (i.e., affective, cognitive, and behavioral learning outcomes). Moderator analyses were conducted using meta-regression, considering factors such as types of learning outcomes, training levels, SRL subscales, and quality of the studies. The analysis yielded an average effect size of .212, using Pearson's correlation coefficient, demonstrating a positive and significant association between SRL strategies and overall learning outcomes. Although our moderator analyses indicated that SRL subscales and study quality did not significantly influence the relationship between SRL strategies and learning outcomes, SRL strategies had a more pronounced effect on affective outcomes than on test scores, behavioral outcomes, and mental health outcomes. In addition, the association between SRL strategies and learning outcomes were significantly higher among the clerkship phase of undergraduate medical education than the pre-clerkship phase.

Construction of covalent organic frameworks via the Mannich reaction at room temperature for light-driven oxidative hydroxylation of arylboronic acids.

An increasing variety of organic reactions have been developed for the synthesis of more structurally stable and multifunctional COFs. Here, we report a class of ß-ketamine linked covalent organic frameworks that were constructed through the CeCl3-catalyzed multi-component Mannich reaction at room temperature. And the TAD-COF obtained based on this method could significantly promote the light-driven oxidative hydroxylation of arylboronic acids.

Astaxanthin Alleviates Chronic Prostatitis via the ERK1/2 Signaling Pathway: Evidence from Network Pharmacology and Experimental Validation.

BACKGROUND: Astaxanthin (AST) has been widely recognized for its therapeutic potential in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP). METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control, complete Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and saline was used for the control group. Inflammation of the prostate was detected 28 days after oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network pharmacology, and related proteins were detected by Western blotting. RESULTS: Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for 48 h were 171 and 212.1 µM, respectively. AST pretreatment reduced IL-6 and IL-8 expression in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory effect of AST was associated with the ERK1/2 pathway. Western blotting showed that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors (U0126) synergistically inhibited LPS-induced inflammation in prostate cells. CONCLUSION: Our study identified the potential of AST in the treatment of CP. However, subsequent randomized controlled trials are needed to validate its clinical efficacy.

Correlation of PSA and survival in metastatic hormone-sensitive prostate cancer treated with rezvilutamide plus ADT in the CHART trial.

BACKGROUND: This exploratory analysis of the CHART trial (ClinicalTrials.gov: NCT03520478) investigated prostate-specific antigen (PSA) kinetics and the correlation between PSA and survival outcomes in high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC). METHODS: A total of 654 patients were randomized 1:1 to receive either rezvilutamide plus androgen deprivation therapy (ADT; n = 326) or bicalutamide plus ADT (n = 328). PSA kinetics were evaluated, and the correlation between survival and the achievement of undetectable PSA (≤0.2 ng/mL) or ≥90% PSA reduction (PSA90) was assessed. FINDINGS: The rezvilutamide group exhibited higher proportions of ≥50% PSA reduction (PSA50; 98.2% vs. 87.5%), PSA90 (88.7% vs. 63.1%), and undetectable PSA (38.3% vs. 17.7%) responses compared to the bicalutamide group by 3 months. The rezvilutamide group demonstrated superior efficacy in delaying PSA progression compared to the bicalutamide group (hazard ratio [HR] 0.21, 95% confidence interval 0.16-0.27). The achievement of undetectable PSA and PSA90 by 6 months in the rezvilutamide group was associated with prolonged overall survival (undetectable PSA, HR = 0.34; PSA90, HR = 0.22), radiographic progression-free survival (HR = 0.36, HR = 0.26), time to PSA progression (HR = 0.25, HR = 0.17), and time to castration resistance (HR = 0.34, HR = 0.23) compared to those who did not achieve these PSA milestones. Stratification by baseline PSA level revealed consistent survival improvements with rezvilutamide plus ADT across quartiles. CONCLUSIONS: PSA kinetics is a valuable prognostic factor in mHSPC treated with rezvilutamide plus ADT, and the achievement of undetectable PSA and PSA90 is associated with improved survival. These findings highlight the importance of monitoring PSA kinetics in the management of mHSPC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Childhood and adolescent essential thrombocythemia and prefibrotic primary myelofibrosis: insights into diagnosis, outcomes, and treatment from a large Chinese cohort.

The paucity of essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) in individuals younger than 18 years highlights several unresolved issues in diagnosis, clinical outcomes, and treatment strategies. To address these knowledge gaps, we analyzed a large bidirectional cohort consisting of childhood and adolescent ET (CAA-ET, n = 156) and pre-PMF (CAA-preMF, n = 13), as well as adult ET (n = 349). We introduced immunophenotypic abnormalities as novel clonal markers in CAA-ET and CAA-preMF, establishing a comprehensive method for clonal marker detection that integrated driver and non-driver mutations, positive endogenous erythroid colony formation, immunophenotypic abnormalities, and chromosomal aberrations. Next-generation sequencing revealed distinct mutational profiles between CAA-ET and adult ET, along with different age-related trends in the distribution of driver mutations. Venous thrombosis was more prevalent in CAA-ET, with JAK2 V617F emerging as a potential risk factor (P = 0.018). Immunophenotypic abnormalities were identified as risk factors for disease progression (P = 0.027). Significant differences between expected and actual treatment practices were identified. Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.

Fe-HCOF-PEG2000 as a Hypoxia-Tolerant Photosensitizer to Trigger Ferroptosis and Enhance ROS-Based Cancer Therapy.

Background: The hypoxic tumor microenvironment and single mechanisms severely limit the photodynamic therapy (PDT) efficiency of covalent organic framework (COF) nanoparticles in cancer treatment. Purpose: Here, we propose an iron-loaded, hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000)-modified hollow covalent organic framework (HCOF), Fe-HCOF-PEG2000, for use in hypoxic PDT and ferroptosis therapy owing to its type I and II photodynamic ability and iron nanoparticle loading property. Results: Fe-HCOF-PEG2000 nanoparticles (Fe-HCOFs-PEG2000) with semiconducting polymers and microporous skeletons allow efficient photophysical properties. Moreover, the iron nanoparticles on Fe-HCOF-PEG2000 caused ferroptosis and further enhanced tumor elimination under normoxic and hypoxic conditions. DSPE-PEG2000 endowed Fe-HCOF-PEG2000 with hydrophilicity, allowing it to circulate and accumulate in organs rich in blood supply, especially tumors. 808 nm NIR activated Fe-HCOF-PEG2000 aggregated in tumors and significantly inhibited tumor growth under hypoxia. Conclusion: To our knowledge, Fe-HCOF-PEG2000 is the leading combination of type I/II PDT and ferroptosis. The strong antitumor effects of this nanomaterial suggest prospects for clinical translation as a tumor nanotherapy drug.

High PD-1 and CTLA-4 expression correlates with host immune suppression in patients and a mouse model infected with Echinococcus multilocularis.

BACKGROUND: Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear. METHODS: We collected liver specimens from hepatic alveolar echinococcosis (HAE) patients and established a mouse model of E. multilocularis infection. Immunofluorescence staining and flow cytometry were performed to analyze programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) expression in human samples, while flow cytometry and quantitative real-time polymerase chain reaction (PCR) were performed for similar analyses in mouse samples. Cell proliferation and protoscolex (PSC) killing assays were designed to explore how E. multilocularis induces host immunosuppression. RESULTS: An inflammatory reaction band with high PD-1 and CTLA-4 expression was found in close liver tissue (CLT). The ratio of regulatory T cells (Tregs) was higher in CLT than in distant liver tissue (DLT), and Tregs in CLT tended to express higher levels of PD-1 and CTLA-4 than those in DLT from HAE patients. Echinococcus multilocularis-infected mice showed significantly elevated expression of PD-1 and CTLA-4 on splenocytes and peritoneal cells. PD-1/PD-L1 or CTLA-4 pathway blockade could relieve the immunosuppressive effects of Tregs from infected mice and enhance PSC killing by mouse splenocytes. CONCLUSIONS: E. multilocularis regulated the function of T cells via the PD-1/PD-L1- and CTLA-4-dependent pathways and subsequently evaded host immune attacks. These findings provide insights for investigating the pathogenic mechanism of AE.

Effects of Nitric Oxide on Bladder Detrusor Overactivity through the NRF2 and HIF-1α Pathways: A Rat Model Induced by Metabolic Syndrome and Ovarian Hormone Deficiency.

Metabolic syndrome (MetS) includes cardiovascular risk factors like obesity, dyslipidemia, hypertension, and glucose intolerance, which increase the risk of overactive bladder (OAB), characterized by urgency, frequency, urge incontinence, and nocturia. Both MetS and ovarian hormone deficiency (OHD) are linked to bladder overactivity. Nitric oxide (NO) is known to reduce inflammation and promote healing but its effect on bladder overactivity in MetS and OHD is unclear. This study aimed to investigate NO's impact on detrusor muscle hyperactivity in rats with MetS and OHD. Female Sprague-Dawley rats were divided into seven groups based on diet and treatments involving L-arginine (NO precursor) and L-NAME (NOS inhibitor). After 12 months on a high-fat, high-sugar diet with or without OVX, a cystometrogram and tracing analysis of voiding behavior were used to identify the symptoms of detrusor hyperactivity. The MetS with or without OHD group had a worse bladder contractile response while L-arginine ameliorated bladder contractile function. In summary, MetS with or without OHD decreased NO production, reduced angiogenesis, and enhanced oxidative stress to cause bladder overactivity, mediated through the NF-kB signaling pathway, whereas L-arginine ameliorated the symptoms of detrusor overactivity and lessened oxidative damage via the NRF2/HIF-1α signaling pathway in MetS with or without OHD-induced OAB.

Drug-Free Mesoporous Silica Nanoparticles Enable Suppression of Cancer Metastasis and Confer Survival Advantages to Mice with Tumor Xenografts.

Despite advancements in nanomedicine for drug delivery, many drug-loaded nanoparticles reduce tumor sizes but often fail to prevent metastasis. Mesoporous silica nanoparticles (MSNs) have attracted attention as promising nanocarriers. Here, we demonstrated that MSN-PEG/TA 25, with proper surface modifications, exhibited unique antimetastatic properties. In vivo studies showed that overall tumor metastasis decreased in 4T1 xenografts mice treated with MSN-PEG/TA 25 with a notable reduction in lung tumor metastasis. In vitro assays, including wound-healing, Boyden chamber, tube-formation, and real-time cell analyses, showed that MSN-PEG/TA 25 could modulate cell migration of 4T1 breast cancer cells and interrupt tube formation by human umbilical vein endothelial cells (HUVECs), key factors in suppressing cancer metastasis. The synergistic effect of MSN-PEG/TA 25 combined with liposomal-encapsulated doxorubicin (Lipo-Dox) significantly boosted mouse survival rates, outperforming Lipo-Dox monotherapy. We attributed the improved survival to the antimetastatic capabilities of MSN-PEG/TA 25. Moreover, Dox-loaded MSN-PEG/TA 25 suppressed primary tumors while retaining the antimetastatic effect, thereby enhancing therapeutic outcomes and overall survival. Western blot and qPCR analyses revealed that MSN-PEG/TA 25 interfered with the phosphorylation of ERK, FAK, and paxillin, thus impacting focal adhesion turnover and inhibiting cell motility. Our findings suggest that drug-free MSN-PEG/TA 25 is highly efficient for cancer treatment via suppressing metastatic activity and angiogenesis.

Graduating Vascular Surgery Trainee Proficiency in Endovascular and Open Peripheral Revascularization Procedures.

INTRODUCTION: Endovascular interventions for peripheral artery disease have increased in prevalence over time given the inherent benefits of minimally invasive approaches. While it is essential that vascular surgery graduates are facile with endovascular techniques, the results of the BEST-CLI trial highlight the equivalent importance of ensuring trainee competence in open skills. Recent studies demonstrate increasing case volume of both endovascular and open procedures during vascular surgery training. Case volume is merely a surrogate marker for competence, however, and the objective competence attained by trainees at the time of graduation is unknown. We sought to investigate operative autonomy and competence of graduating vascular surgery trainees performing endovascular as compared to open peripheral vascular revascularization procedures. METHODS: Operative performance and autonomy ratings for infrainguinal endovascular and open revascularizations from the Society for Improving Professional Learning Operative (SIMPL OR) application database were collected for all vascular surgery participating institutions from 2018-23. The distribution for autonomy and performance ratings were determined by training level for endovascular and open procedures, respectively. Mixed effects logistic regressions were conducted to estimate the predictive association between procedure type and autonomy and performance assessment, adjusting for training level and case complexity. Subsequently, the estimated model was applied to predict the probability of a graduating trainee being rated as meaningfully autonomous or competent while performing endovascular and open procedures across various case complexities. RESULTS: Sixty-nine residents from 23 programs (12 fellowship, 11 residency) were assessed on 706 revascularization procedures (n=383 endovascular, 323 open). When controlling for training level and case complexity, there were no differences in autonomy (OR 1.11 [95% CI: 0.62-1.99]) or competency assessment (OR 0.86 [95% CI: 0.46-1.59]) for endovascular, as compared to open, peripheral revascularization procedures. For average complexity procedures, the predicted probability of a trainee being assessed as competent and autonomous at the time of graduation was high (competent: 88% endovascular, 86% open; autonomous: 96% endovascular, 97% open). Predicted probability of competence and autonomy for complex procedures was lower but remained similar between groups (competent:73% endovascular, 70% open; autonomous: 92% endovascular, 92% open). CONCLUSIONS: There is no difference in the graduating level of autonomy and competence of endovascular as compared to open peripheral revascularization procedures for vascular surgery trainees. These findings suggest vascular surgery trainees enter independent practice with adequate proficiency to utilize the full scope of techniques to care for patients requiring peripheral revascularization procedures.

Nanotechnology based gas delivery system: a "green" strategy for cancer diagnosis and treatment.

Gas therapy, a burgeoning clinical treatment modality, has garnered widespread attention to treat a variety of pathologies in recent years. The advent of nanoscale gas drug therapy represents a novel therapeutic strategy, particularly demonstrating immense potential in the realm of oncology. This comprehensive review navigates the landscape of gases endowed with anti-cancer properties, including hydrogen (H2), carbon monoxide (CO), carbon dioxide (CO2), nitric oxide (NO), oxygen (O2), sulfur dioxide (SO2), hydrogen sulfide (H2S), ozone (O3), and heavier gases. The selection of optimal delivery vectors is also scrutinized in this review to ensure the efficacy of gaseous agents. The paper highlights the importance of engineering stimulus-responsive delivery systems that enable precise and targeted gas release, thereby augmenting the therapeutic efficiency of gas therapy. Additionally, the review examines the synergistic potential of integrating gas therapy with conventional treatments such as starvation therapy, ultrasound (US) therapy, chemotherapy, radiotherapy (RT), and photodynamic therapy (PDT). It also discusses the burgeoning role of advanced multimodal and US imaging in enhancing the precision of gas therapy applications. The insights presented are pivotal in the strategic development of nanomedicine platforms designed for the site-specific delivery of therapeutic gases, heralding a new era in cancer therapeutics.

Reduced platelet activation in triple-negative essential thrombocythemia compared with JAK2V617F-mutated essential thrombocythemia.

PURPOSE: Triple-negative (TN) essential thrombocytopenia (ET) is characterized by the absence of driver mutations while retaining histological and phenotypic characteristics sufficient for an ET diagnosis. Our understanding of TN-ET and its platelet activation remains incomplete. We carried out a large-scale multi-center clinical analysis to analyze the clinical and molecular characteristics, thrombotic complications of TN-ET. We also related the above characteristics to platelet activation to further explore the thrombosis mechanism of TN-ET. EXPERIMENTAL DESIGN: A retrospective multicenter study was conducted on 138 TN-ET and 759 ET patients with driver mutations from 1 March 2012 to 1 December 2021. The clinical and molecular characteristics of the TN-ET were summarized. Additionally, platelet activation, apoptosis, and reactive oxygen species (ROS) levels were analyzed in 73 TN-ET patients from this cohort and compared to 41 age- and sex-matched healthy donors. RESULTS: Compared to patients with the JAK2V617F mutation, those with triple-negative mutation were younger (P < 0.001) and exhibited fewer thrombotic events before diagnosis (P < 0.001) and during follow-up (P = 0.039). Patients with triple-negative mutation also presented with significantly reduced CD62P expression in platelets (P = 0.031), slightly reduced calcium concentration in platelets (P = 0.063), increased mitochondrial membrane potential (P = 0.011), reduced phosphatidylserine exposure (P = 0.015), reduced levels of ROS (P = 0.043) and MitoSOX in platelets (P = 0.047). CONCLUSIONS: In comparison to JAK2V617F-mutated ET, TN-ET is associated with lower platelet ROS levels, which leads to reduced platelet activation and consequently a lower risk of thrombosis.

Vkorc1 polymorphisms of the Norway rats in China: Implications for rodent management and evolutionary origin of anticoagulant resistance mutations.

The extensive utilization of second-generation anticoagulant rodenticides (SGARs) has raised concerns regarding non-target animal safety and environmental contamination. It is essential to assess the anticoagulant resistance level in rodent populations and prioritize the use of relative low toxic first-generation anticoagulant rodenticides (FGARs) in susceptible rodent populations. Mutations in the vitamin K epoxide reductase complex subunit 1 (Vkorc1) gene confer anticoagulant resistance in Norway rats. However, the Vkorc1 polymorphisms remain unclear in most Norway rat populations in China although anticoagulant rodenticides have been widely used in China since the 1980s. Analysis of the Vkorc1 polymorphisms in 489 rats across China, combined with in silico binding affinity analysis, revealed three potential resistance mutations A26T, C96Y, and A140T at three distinct locations. In the remaining locations, Vkorc1 resistance mutations were absent, indicating that the FGARs could be effective in these areas. Additional evolutionary analysis of different Vkorc1 mutations suggested that the three missense mutations identified in China might have evolved independently as de novo mutations, and the resistance mutations in Europe are unlikely to be pre-existing variations in China. Further analysis of Vkorc1 haplotypes among European resistant rat populations is essential for understanding the origin of these resistance mutations. These findings emphasize the importance of customizing rodent control strategies in China based on regional resistance levels and gaining insights into the origins of Vkorc1 mutations for more effective rodent management strategies.

Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.

Ovarian cancer is a common cancer for females, and the incidence and mortality rates are on the rise. Many treatment strategies have been developed for ovarian cancer, including chemotherapy and immunotherapy, but they are often ineffective and prone to drug resistance. Protein ubiquitination is an important class of post-translation modifications that have been found to be associated with various human diseases and cancer development. Recent studies have revealed that protein ubiquitination is involved in the progression of ovarian cancer and plays an important role in the tumor immune process. Moreover, the combination of ubiquitinase/deubiquitinase inhibitors and cancer immunotherapy approaches can effectively reduce treatment resistance and improve treatment efficacy, which provides new ideas for cancer treatment. Herein, we review the role of protein ubiquitination in relation to ovarian cancer immunotherapy and recent advances in the use of ubiquitinase/deubiquitinase inhibitors in combination with cancer immunotherapy.

Black phosphorus for bone regeneration: Mechanisms involved and influencing factors.

BP has shown good potential for promoting bone regeneration. However, the understanding of the mechanisms of BP-enhanced bone regeneration is still limited. This review first summarizes the recent advances in applications of BP in bone regeneration. We further highlight the possibility that BP enhances bone regeneration by regulating the behavior of mesenchymal stem cells (MSCs), osteoblasts, vascular endothelial cells (VECs), and macrophages, mainly through the regulation of cytoskeletal remodeling, energy metabolism, oxidation resistance and surface adsorption properties, etc. In addition, moderating the physicochemical properties of BP (i.e., shape, size, and surface charge) can alter the effects of BP on bone regeneration. This review reveals the underlying mechanisms of BP-enhanced bone regeneration and provides strategies for further material design of BP-based materials for bone regeneration.

The association between child maltreatment, cognitive reappraisal, negative coping styles, and non-suicidal self-injury in adolescents with major depressive disorder.

BACKGROUND: Non-suicidal self-injury (NSSI) is a significant public health concern among adolescents with major depressive disorders (MDD). Although previous research has linked child maltreatment (CM) to NSSI, the precise mechanisms remain unclear. This study aims to investigate the association between CM, cognitive reappraisal (CR), negative coping styles (NC) and NSSI in adolescents with MDD, from the perspectives of both Latent Variable Theory and the Network Theory of Mental Disorder. METHODS: A sample of 651 adolescents with MDD was recruited from January to December 2023. Data on CM, CR, NC, and NSSI were collected through paper-based self-reported questionnaires. Data analysis primarily involved structural equation modeling and network analysis. RESULTS: The reporting rate of NSSI among adolescents with MDD was 48.2%. CM showed a significant positive correlation with NSSI. NSSI was affected by CM through three paths: the mediating role of CR, the mediating role of NC, and the chain mediating role of both CR and NC. Emotional abuse (EA) was the central node, while NSSI, EA, and "The urge to cry quietly when faced with troubles"(NC10) were the key bridge nodes. CONCLUSIONS: This study is the first to use both structural equation modeling and network analysis to explore the explore the relationship between CM, CR, NC, and NSSI in adolescents with MDD, providing a theoretical basis for future early prevention and targeted interventions for adolescents with MDD.

Reliability of a workplace-based assessment for the United States general surgical trainees' intraoperative performance using multivariate generalizability theory: a psychometric study

PURPOSE: The System for Improving and Measuring Procedure Learning (SIMPL), a smartphone-based operative assessment application, was developed to assess the intraoperative performance of surgical residents. This study aims to examine the reliability of the SIMPL assessment and determine the optimal number of procedures for a reliable assessment. METHODS: In this retrospective observational study, we analyzed data collected between 2015 and 2023 from 4,616 residents across 94 General Surgery Residency programs in the United States that utilized the SIMPL smartphone application. We employed multivariate generalizability theory and initially conducted generalizability studies to estimate the variance components associated with procedures. We then performed decision studies to estimate the reliability coefficient and the minimum number of procedures required for a reproducible assessment. RESULTS: We estimated that the reliability of the assessment of surgical trainees' intraoperative autonomy and performance using SIMPL exceeded 0.70. Additionally, the optimal number of procedures required for a reproducible assessment was 10, 17, 15, and 17 for postgraduate year (PGY) 2, PGY 3, PGY 4, and PGY 5, respectively. Notably, the study highlighted that the assessment of residents in their senior years necessitated a larger number of procedures compared to those in their junior years. CONCLUSION: The study demonstrated that the SIMPL assessment is reliably effective for evaluating the intraoperative performance of surgical trainees. Adjusting the number of procedures based on the trainees' training stage enhances the assessment process's accuracy and effectiveness.

A single-center study of patients with rare isolated acquired clotting factor deficiencies other than acquired hemophilia A.

Background: Isolated acquired clotting factor deficiencies (ACFDs) are mainly caused by the existence of anti-factor antibodies or adsorption of clotting factors onto substances such as amyloid. Besides acquired factor (F)VIII deficiency (acquired hemophilia A), the remaining factor deficiencies are rare and diverse, posing challenges in both diagnosis and management. Objectives: To describe different features of isolated ACFDs to improve our understanding of these diseases and provide practical recommendations for their management. Methods: Clinical characteristics of patients with isolated acquired FII, FV, FIX, FX, FXI, FXII, FXIII, and von Willebrand factor deficiencies were collected from a single center between July 1997 and December 2021 and analyzed retrospectively. Results: A total of 54 rare isolated ACFD patients were enrolled in our study, mainly including 20 acquired FV deficiency patients and 16 acquired FX deficiency patients. The median age at diagnosis of all rare isolated ACFD patients was 55 years. The median time to diagnose all rare isolated ACFD patients was 60 days. Ten (18.5%) rare isolated ACFD patients had no bleeding and 2 (3.7%) rare isolated ACFD patients showed venous thromboembolism. Hemostatic treatment was applied to 41 (41/54; 75.9%) rare isolated ACFD patients. Thirty-seven (68.5%) rare isolated ACFD patients received immunosuppressive therapy, and 10 (18.5%) rare isolated ACFD patients received chemotherapy targeting primary diseases. Twenty-two (61.9%) rare isolated ACFD patients achieved complete remission, and 9 (21.4%) rare isolated ACFD patients died. Conclusion: Rare isolated ACFDs are underestimated, associated with delayed diagnosis, and lack effective therapy. Clinicians should raise awareness for recognizing and managing rare isolated ACFD patients to avoid morbidity and mortality.