A nomogram with Nottingham prognostic index for predicting locoregional recurrence in breast cancer patients.

Background: The Nottingham prognostic index (NPI) has been shown to negatively impact survival in breast cancer (BC). However, its ability to predict the locoregional recurrence (LRR) of BC remains still unclear. This study aims to determine whether a higher NPI serves as a significant predictor of LRR in BC. Methods: In total, 238 patients with BC were included in this analysis, and relevant clinicopathological features were collected. Correlation analysis was performed between NPI scores and clinicopathological characteristics. The optimal nomogram model was determined by Akaike information criterion. The accuracy of the model's predictions was evaluated using receiver operating characteristic curves (ROC curves), calibration curves and goodness of fit tests. The clinical application value was assessed through decision curve analysis. Results: Six significant variables were identified, including age, body mass index (BMI), TNM stage, NPI, vascular invasion, perineural invasion (P<0.05). Two prediction models, namely a TNM-stage-based model and an NPI-based model, were constructed. The area under the curve (AUC) for the TNM-stage- and NPI-based models were 0.843 (0.785,0.901) and 0.830 (0.766,0.893) in training set and 0.649 (0.520,0.778) and 0.728 (0.610,0.846) in validation set, respectively. Both models exhibited good calibration and goodness of fit. The F-measures were 0.761vs 0.756 and 0.556 vs 0.696, respectively. Clinical decision curve analysis showed that both models provided clinical benefits in evaluating risk judgments based on the nomogram model. Conclusions: a higher NPI is an independent risk factor for predicting LRR in BC. The nomogram model based on NPI demonstrates good discrimination and calibration, offering potential clinical benefits. Therefore, it merits widespread adoption and application.

Association of preoperative frailty with risk of postoperative delirium in older patients undergoing craniotomy: a prospective cohort study.

BACKGROUND: Preoperative frailty is a risk factor associated with postoperative delirium (POD), which has attracted more attention from clinicians, but no research has shown that it is related to elderly patients undergoing craniotomy. Therefore, the aim of this study was to determine the effect of preoperative frailty on POD in older patients, especially those who underwent craniotomy. METHODS: From October 2022 to May 2023, older patients who underwent elective craniotomy were collected. Assess the occurrence of frailty using the FRAIL scale one day before surgery. Evaluate the occurrence of POD using the Confusion Assessment Method (CAM) within three days after surgery. Participants were divided into two groups, one group being POD, Logistic regression analysis was used to find the risk variables for POD, and the predictive value of preoperative frailty to POD was determined by using the operating characteristic curve of the subjects. RESULTS: A total of 300 patients were included in this study, among whom 83 patients (27.7%) exhibited preoperative frailty and 69 patients (23.0%) experienced POD. The results of the multivariate logistic regression analysis indicate that preoperative frailty (OR: 8.816, 95% CI: 3.972-19.572), preoperative hypoalbuminemia (OR: 0.893, 95% CI: 0.811-0.984), low BMI (OR: 0.793, 95% CI: 0.698-0.901), and prolonged operative duration (OR: 1.007, 95% CI: 1.004-1.010) are independent risk factors for POD in older patients who underwent craniotomy. We constructed a risk prediction model using these factors, which had an area under the ROC curve of 0.908 (95% CI: 0.869-0.947, P < 0.001). Preoperative frailty enhanced the discriminative ability of the prediction model by 0.037. POD was associated with a longer length of hospital stay and higher hospitalization costs. CONCLUSIONS: Preoperative frailty is an independent risk factor for POD in older patients undergoing elective craniotomy and can predict the occurrence of POD to a certain extent. In addition, early identification of patients at risk of malnutrition and appropriate surgical planning can reduce the incidence of POD.

A biomimic anti-neuroinflammatory nanoplatform for active neutrophil extracellular traps targeting and spinal cord injury therapy.

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI.

Resveratrol Alleviated T-2 Toxin-Induced Liver Injury via Preservation of Nrf2 Pathway and GSH Synthesis.

T-2 toxin is a trichothecene mycotoxin and is considered as an extremely inevitable pollutant with potent hepatotoxicity. However, the approach to alleviation of T-2 toxin-triggered hepatotoxicity has been recognized as a serious challenge. Resveratrol (Res) is a polyphenol natural product isolated from various plant species, but its protective effect against T-2 toxin hepatotoxicity and detailed mechanism remains obscure. In the present study, the effect of Res against the hepatotoxicity was evaluated, and the underlying mechanisms were further revealed in mice. Functionally, Res inhibited liver injury, oxidative damage, and mitochondrial dysfunction induced by T-2 toxin. Mechanistically, Res modulated Nrf2-mediated antioxidant pathway and glutathione synthesis inhibition. Collectively, our findings first showed beyond doubt that Res ameliorated T-2 toxin-triggered liver injury by regulating Nrf2 pathways in mice.

Exploring the correlation between homocysteine, red blood cell folate and MTHFRC677T genotypes with female infertility.

Aim: To investigate the association between serum homocysteine (HCY) levels, red blood cell folate (RCF) levels, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and infertility.Materials & methods: Serum HCY and RCF levels and C677T polymorphism of MTHFR gene were analyzed in 149 infertile patients and 223 women of normal reproductive age with healthy childbirth history.Results: The HCY level of MTHFR C677T TT genotype infertility patients was higher than that of women of normal reproductive age, while the RCF level was not significantly different between the two groups.Conclusion: Serum HCY levels increased in infertility patients, and the MTHFR C677T TT genotype in childbearing-aged women are associated with a higher risk of infertility. The results showed that HCY level and MTHFR C677T genotype were closely related to infertility.

[Box: see text].

Improving Image Quality and Diagnostic Performance of CCTA in Patients with Challenging Heart Rate Conditions Using a Deep Learning-Based Motion Correction Algorithm.

OBJECTIVE: Challenging HR conditions, such as elevated Heart Rate (HR) and Heart Rate Variability (HRV), are major contributors to motion artifacts in Coronary Computed Tomography Angiography (CCTA). This study aims to assess the impact of a deep learning-based motion correction algorithm (MCA) on motion artifacts in patients with challenging HR conditions, focusing on image quality and diagnostic performance of CCTA. MATERIALS AND METHODS: This retrospective study included 240 patients (mean HR: 88.1 ± 14.5 bpm; mean HRV: 32.6 ± 45.5 bpm) who underwent CCTA between June, 2020 and December, 2020. CCTA images were reconstructed with and without the MCA. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured to assess objective image quality. Subjective image quality was evaluated by two radiologists using a 5-point scale regarding vessel visualization, diagnostic confidence, and overall image quality. Moreover, all vessels with scores ≥ 3 were considered clinically interpretable. The diagnostic performance of CCTA with and without MCA for detecting significant stenosis (≥ 50%) was assessed in 34 patients at both per-vessel and per-patient levels, using invasive coronary angiography as the reference standard. RESULTS: The MCA significantly improved subjective image quality, increasing the vessel interpretability from 89.9% (CI: 0.88-0.92) to 98.8% (CI: 0.98-0.99) (p < 0.001). The use of MCA resulted in significantly higher diagnostic performance in both patient-based (AUC: 0.83 vs. 0.58, p = 0.04) and vessel-based (AUC: 0.92 vs. 0.81, p < 0.001) analyses, with the vessel-based accuracy notably increased from 79.4% (CI: 0.72-0.86) to 91.2% (CI: 0.85-0.95) (p = 0.01). There were no significant differences in objective image quality between the two reconstructions. The mean effective dose in this study was 2.8 ± 1.1 mSv. CONCLUSION: The use of MCA allows for obtaining high-quality CCTA images and superior diagnostic performance with low radiation exposure in patients with elevated HR and HRV.

A LBD transcription factor from moso bamboo, PheLBD12, regulates plant height in transgenic rice.

The regulation mechanism of bamboo height growth has always been one of the hotspots in developmental biology. In the preliminary work of this project, the function of LBD transcription factor regulating height growth was firstly studied. Here, a gene PheLBD12 regulating height growth was screened. PheLBD12-overexpressing transgenic rice had shorter internodes, less bioactive gibberellic acid (GA3), and were more sensitive to GA3 than wild-type (WT) plants, which implied that PheLBD12 involve in gibberellin (GA) pathway. The transcript levels of OsGA2ox3, that encoding GAs deactivated enzyme, was significantly enhanced in PheLBD12-overexpressing transgenic rice. The transcript levels of OsAP2-39, that directly regulating the expression of EUI1 to reduce GA levels, was also significantly enhanced in PheLBD12-overexpressing transgenic rice. Expectedly, yeast one-hybrid assays, Dual-luciferase reporter assay and EMSAs suggested that PheLBD12 directly interacted with the promoter of OsGA2ox3 and OsAP2-39. Together, our results reveal that PheLBD12 regulates plant height growth by modulating GA catabolism. Through the research of this topic, it enriches the research content of LBD transcription factors and it will theoretically enrich the research content of height growth regulation.

Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) represents an autoimmune disorder that affects multiple systems. In the treatment of this condition, the focus primarily revolves around inflammation suppression and immunosuppression. Consequently, targeted therapy has emerged as a prevailing approach. Currently, the quest for highly sensitive and specifically effective targets has gained significant momentum in the context of SLE treatment. Lymphocyte activation gene-3 (LAG-3) stands out as a crucial inhibitory receptor that binds to pMHC-II, thereby effectively dampening autoimmune responses. Fibrinogen-like protein 1 (FGL1) serves as the principal immunosuppressive ligand for LAG-3, and their combined action demonstrates a potent immunosuppressive effect. This intricate mechanism paves the way for potential SLE treatment by targeting LAG-3 with FGL1. This work provides a comprehensive summary of LAG-3's role in the pathogenesis of SLE and elucidates the feasibility of leveraging FGL1 as a therapeutic approach for SLE management. It introduces a novel therapeutic target and opens up new avenues of therapeutic consideration in the clinical context of SLE treatment.

Acceleration of Orthodontic Tooth Movement: A Bibliometric and Visual Analysis.

BACKGROUND: Prolonged orthodontic treatment duration has long been a concern for orthodontists and patients, leading to a surge in publications on accelerated orthodontic tooth movement (OTM). This study aims to investigate the knowledge landscape, hotspots, and research trends in acceleration of OTM using bibliometric and visual analyses. METHODS: A comprehensive search was conducted in the Web of Science (WOS) Core Collection to identify relevant publications related to acceleration of OTM. R Biblioshiny, VOS viewer, and a bibliometric online analysis platform were used to conduct the bibliometric and visualization analysis. Curve fitting and correlation analysis were performed to examine the correlation global and country economics and publication trends, and to predict publication numbers. RESULTS: A total of 647 articles on accelerated OTM were included in the analysis, with clinical and non-clinical publications accounting for 43.59% and 31.22%, respectively. The annual publication numbers exhibited an upward trend, correlating positively with both global gross domestic product (GDP) (r = 0.915, P < .001) and the GDP of individual countries/regions (r = 0.976, P < .001). China produced the most documents (94), while the USA led in citation count (2758) and international collaborations. Wilcko WM was the top-cited author, with eight of the top 10 authors from the USA and the remainder from Asia. Keywords such as 'tooth movement', 'corticotomy', 'piezocision' and 'low-level laser therapy' were the most prominent themes, while topics like 'micro-osteoperforation', 'plasma', 'gingival crevicular fluid' and 'pain' have become recent research hotspots and frontiers. CONCLUSIONS: This study provides a comprehensive overview of the research on accelerated OTM, highlighting hotspots and frontiers, fostering collaboration among authors and countries/regions, and contributing to future research endeavours.

Predictive Analysis in Oral Cancer Immunotherapy: Profiling Dual PD-L1-Positive Extracellular Vesicle Subtypes with Step-Wedge Microfluidic Chips.

PD-L1-positive extracellular vesicles (PD-L1+ EVs) play a pivotal role as predictive biomarkers in cancer immunotherapy. These vesicles, originating from immune cells (I-PD-L1+ EVs) and tumor cells (T-PD-L1+ EVs), hold distinct clinical predictive values, emphasizing the importance of deeply differentiating the PD-L1+ EV subtypes for effective liquid biopsy analyses. However, current methods such as ELISA lack the ability to differentiate their cellular sources. In this study, a novel step-wedge microfluidic chip that combines magnetic microsphere separation with single-layer fluorescence counting is developed. This chip integrates magnetic microspheres modified with anti-PD-L1 antibodies and fluorescent nanoparticles targeting EpCAM (tumor cell marker) or CD45 (immunocyte marker), enabling simultaneous quantification and sensitive analysis of PD-L1+ EV subpopulations in oral squamous cell carcinoma (OSCC) patients' saliva without background interference. Analysis results indicate reduced levels of I-PD-L1+ EVs in OSCC patients compared to those in healthy individuals, with varying levels of heterogeneous PD-L1+ EVs observed among different patient groups. During immunotherapy, responders exhibit decreased levels of total PD-L1+ EVs and T-PD-L1+ EVs, accompanied by reduced levels of I-PD-L1+ EVs. Conversely, nonresponders show increased levels of I-PD-L1+ EVs. Utilizing the step-wedge microfluidic chip allows for simultaneous detection of PD-L1+ EV subtypes, facilitating the precise prediction of oral cancer immunotherapy outcomes.

MolMVC: Enhancing molecular representations for drug-related tasks through multi-view contrastive learning.

MOTIVATION: Effective molecular representation is critical in drug development. The complex nature of molecules demands comprehensive multi-view representations, considering 1D, 2D, and 3D aspects, to capture diverse perspectives. Obtaining representations that encompass these varied structures is crucial for a holistic understanding of molecules in drug-related contexts. RESULTS: In this study, we introduce an innovative multi-view contrastive learning framework for molecular representation, denoted as MolMVC. Initially, we use a Transformer encoder to capture 1D sequence information and a Graph Transformer to encode the intricate 2D and 3D structural details of molecules. Our approach incorporates a novel attention-guided augmentation scheme, leveraging prior knowledge to create positive samples tailored to different molecular data views. To align multi-view molecular positive samples effectively in latent space, we introduce an adaptive multi-view contrastive loss (AMCLoss). In particular, we calculate AMCLoss at various levels within the model to effectively capture the hierarchical nature of the molecular information. Eventually, we pre-train the encoders via minimizing AMCLoss to obtain the molecular representation, which can be used for various down-stream tasks. In our experiments, we evaluate the performance of our MolMVC on multiple tasks, including molecular property prediction (MPP), drug-target binding affinity (DTA) prediction and cancer drug response (CDR) prediction. The results demonstrate that the molecular representation learned by our MolMVC can enhance the predictive accuracy on these tasks and also reduce the computational costs. Furthermore, we showcase MolMVC's efficacy in drug repositioning across a spectrum of drug-related applications. AVAILABILITY AND IMPLEMENTATION: The code and pre-trained model are publicly available at https://github.com/Hhhzj-7/MolMVC.

CLigOpt: controllable ligand design through target-specific optimization.

MOTIVATION: A key challenge in deep generative models for molecular design is to navigate random sampling of the vast molecular space, and produce promising molecules that strike a balance across multiple chemical criteria. Fragment-based drug design (FBDD), using fragments as starting points, is an effective way to constrain chemical space and improve generation of biologically active molecules. Furthermore, optimization approaches are often implemented with generative models to search through chemical space, and identify promising samples which satisfy specific properties. Controllable FBDD has promising potential in efficient target-specific ligand design. RESULTS: We propose a controllable FBDD model, CLigOpt, which can generate molecules with desired properties from a given fragment pair. CLigOpt is a variational autoencoder-based model which utilizes co-embeddings of node and edge features to fully mine information from molecular graphs, as well as a multi-objective Controllable Generation Module to generate molecules under property controls. CLigOpt achieves consistently strong performance in generating structurally and chemically valid molecules, as evaluated across six metrics. Applicability is illustrated through ligand candidates for hDHFR and it is shown that the proportion of feasible active molecules from the generated set is increased by 10%. Molecular docking and synthesizability prediction tasks are conducted to prioritize generated molecules to derive potential lead compounds. AVAILABILITY AND IMPLEMENTATION: The source code is available via  https://github.com/yutongLi1997/CLigOpt-Controllable-Ligand-Design-through-Target-Specific-Optimisation.

TaqMan qPCR and IgM Detection in Samples of Patients with Tick-Borne Encephalitis Virus Infection in Northeast China.

Purpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study. Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics. Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients. Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.

Three-way interaction effect of hindrance research stressors, inclusive mentoring style, and academic resilience on research creativity among doctoral students from China.

With the increasingly intense academic competition, the stressors faced by doctoral students are gradually escalating. Based on the Job Demands-Resources Model, this study proposed a moderated moderation to explore how hindrance research stressors affect doctoral students' research creativity. Explicitly, the present study investigates whether the relationship between hindrance research stressors and research creativity is contingent on inclusive mentoring style and academic resilience. By analyzing the survey data from 538 valid questionnaire responses of doctoral students in China, this study has revealed that hindrance research stressors negatively relate to doctoral students' research creativity, and inclusive mentoring style from academic supervisors can mitigate the negative impact of hindrance research stressors on the research creativity of doctoral students. Furthermore, academic resilience strengthens the moderating effect of inclusive mentoring style. Specifically, it buffers the negative impact of hindrance research stressors on research creativity among doctoral students who receive high inclusive mentoring, but not among those with low levels of inclusive mentoring. These findings emphasize that effective strategies to enhance the research creativity of doctoral students who encounter hindrance stressors may require the joint consideration of contextual and personal resources.

Single-Dose Tolerability and Pharmacokinetics of Onradivir in Chinese Patients with Hepatic Impairment and Healthy Matched Controls.

This study compared the safety and pharmacokinetics of a single oral dose of onradivir, an inhibitor of polymerase basic protein 2 in influenza A virus, in patients with hepatic impairment and healthy participants with normal hepatic function. Eight participants with mild hepatic impairment (Child-Pugh A), eight participants with moderate hepatic impairment (Child-Pugh B), and eight healthy matched controls were enrolled in this open-label, parallel-group clinical trial. After the administration of 600 mg of onradivir, pharmacokinetic parameters were calculated for each cohort and compared. Onradivir was generally well tolerated by all participants. No serious adverse events (AEs) and no deaths were reported during the study. Six patients with moderate hepatic impairment and three patients with mild hepatic impairment reported AEs, all of which were mild and quickly resolved. Compared with the normal liver function group, the maximum concentration, area under the curve from time zero to the last measurable concentration, and area under the curve from time zero to infinity were 103%, 68.5%, and 69.2% higher, respectively, in the mild hepatic impairment group. In the moderate hepatic impairment group, these increases were 101%, 197%, and 204%, respectively. Overall, there were clinically relevant differences in onradivir exposure between patients with mild or moderate hepatic impairment and normal controls. These data imply that onradivir dose adjustment is warranted in patients with mild or moderate hepatic impairment. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05856513).

Lighting Up Nonemissive Azobenzene Derivatives by Pressure.

Pressure-induced emission (PIE) is a compelling phenomenon that can activate luminescence within nonemissive materials. However, PIE in nonemissive organic materials has never been achieved. Herein, we present the first observation of PIE in an organic system, specifically within nonemissive azobenzene derivatives. The emission of 1,2-bis(4-(anthracen-9-yl)phenyl)diazene was activated at 0.52 GPa, primarily driven by local excitation promotion induced by molecular conformational changes. Complete photoisomerization suppression of the molecule was observed at 1.5 GPa, concurrently accelerating the emission enhancement to 3.53 GPa. Differing from the key role of isomerization inhibition in conventional perception, our findings demonstrate that the excited-state constituent is the decisive factor for emission activation, providing a potentially universal approach for high-efficiency azobenzene emission. Additionally, PIE was replicated in the analogue 1,2-bis(4-(9H-carbazol-9-yl)phenyl)diazene, confirming the general applicability of our findings. This work marks a significant breakthrough within the PIE paradigm and paves the novel high-pressure route for crystalline-state photoisomerization investigation.

Microbial Heterogeneity Identification of Cerebral Thrombi Via Metagenomic Next-Generation Sequencing-Based Strategy.

BACKGROUND: Diagnosis of the cause of cerebral thrombi is vital for recurrence prevention but also challenging. The presence of the microbiome has recently been confirmed in thrombus, suggesting a novel approach to distinguish cerebral thrombi of different origins. However, little is known about whether there is heterogeneity in microbiological colonization of cerebral thrombi of different sources. METHODS AND RESULTS: Forty patients experiencing acute ischemic stroke were included and clinical data were collected. Metagenomic next-generation sequencing was adopted to detect bacterial and genomic signatures of human cerebral thrombi samples. We found similar species diversity between the large-artery atherosclerosis thrombi and cardioembolic thrombi but different species composition and distribution of cerebral thrombus microbiota. Compared with the group with cardioembolism, the group with large-artery atherosclerosis showed a significantly higher relative abundance of Ralstonia insidiosa among the top 10 bacterial species in cerebral thrombi. Twenty operational taxonomy units were correlated with 11 clinical indicators of ischemic stroke. The Gene Ontology enrichment analysis revealed 9 different enriched biological processes (translation and carbohydrate metabolic process, etc). The enriched Kyoto Encyclopedia of Genes and Genomes pathways included ribosome, butanoate metabolism, and sulfur metabolism. CONCLUSIONS: This study, based on the approach of metagenomic next-generation sequencing, provides a diagnostic microbiological method to discriminate individuals with cardioembolic thrombi from those with large-artery atherosclerosis thrombi with human cerebral thrombi samples. Our findings provide a fresh perspective on microbial heterogeneity of cerebral thrombi and demonstrate biological processes and pathway features of cerebral thrombi.

Patient-reported outcomes measure for patients with cleft palate.

Cleft palate presents multifaceted challenges impacting speech, hearing, appearance, and cognition, significantly affecting patients' quality of life (QoL). While surgical advancements aim to restore function and improve appearance, traditional clinical measures often fail to comprehensively capture patients' experiences. Patient-reported outcomes measure (PROMs) have emerged as crucial tools in evaluating QoL, offering insights into various aspects such as esthetic results, speech function, and social integration. This review explores PROMs relevant to cleft palate complications, including velopharyngeal insufficiency, oronasal fistulas, maxillary hypoplasia, sleep-disordered breathing, and caregiver QoL. Additionally, the review highlights the need for cleft palate-specific scales to better address the unique challenges faced by patients. By incorporating PROMs, healthcare providers can achieve more personalized, patient-centered care, improve communication, and enhance treatment outcomes. Future research should focus on developing and validating specialized PROMs to further refine patient assessments and care strategies.

[Experiences with the infra-acetabular screw placement technique in acetabular fracture surgery].

Objective: To investigate the application experiences and effectiveness of the infra-acetabular screw (IAS) placement technique in acetabular fracture surgery. Methods: A clinical data of 34 patients with complex acetabular fractures with anterior and posterior columns separation, who were admitted between January 2019 and October 2023 and treated with IAS fixation, was retrospectively analyzed. There were 23 males and 11 females with an average age of 55.3 years (range, 18-78 years). The acetabular fractures caused by traffic accident in 20 cases, falling from height in 12 cases, crushing injury in 1 case, and bruising with a heavy object in 1 case. According to the Letournel-Judet classification, there were 7 cases of anterior column fracture, 8 cases of anterior wall/column plus posterior hemi-transverse fracture, 2 cases of T-shaped fracture, and 17 cases of both-column fracture. The time from injury to surgery was 4-21 days (mean, 8.6 days). The time of IAS placement and the intraoperative blood loss were recorded. After surgery, the X-ray film and CT scan were re-examined, and the modified Matta score was used to assess the quality of fracture reduction. The trajectory of IAS in the channel was analyzed based on CT scan, and the screw length was measured. During follow-up, the fracture healing was observed and the hip function was assessed according to the modified Merle d'Aubigné-Postel scoring system at last follow-up. Results: The IAS was successfully implanted in all 34 patients. The length of IAS ranged from 70 to 100 mm (mean, 86.2 mm). The time of IAS placement ranged from 10 to 40 minutes (mean, 20.7 minutes). The intraoperative blood loss ranged from 520 to 820 mL (mean, 716.8 mL). All patients were followed up 8-62 months (mean, 21.8 months). After surgery, 4 patients developed lateral femoral cutaneous nerve injury, 2 developed popliteal vein thrombosis of the lower extremity, 3 developed incision infection, and no surgical complication such as arteriovenous injury or obturator nerve palsy occurred. At last follow-up, the hip function was rated as excellent in 14 cases, good in 13 cases, fair in 4 cases, and poor in 3 cases according to the Merle d'Aubigné-Postel scoring system, with an excellent and good rate of 79.41%. Imaging re-examined showed that the quality of fracture reduction was rated as excellent in 9 cases, good in 19 cases, and poor in 6 cases according to the modified Matta score, with an excellent and good rate of 82.35%; and 25 (73.53%) IAS trajectories were located in the channel. All fractures obtained bony union, and the healing time was 12-24 weeks (mean, 18 weeks). During follow-up, there was no loosening or fracture of the plate and screws. Conclusion: IAS placement technique can effectively strengthen internal fixation and prevent fracture re-displacement, making it a useful adjunct for treating complex acetabular fractures with anterior and posterior columns separation.

CTGF regulated by ATF6 inhibits vascular endothelial inflammation and reduces hepatic ischemia-reperfusion injury.

Vascular endothelial inflammation is crucial in hepatic ischemia-reperfusion injury (IRI). Our previous research has shown that connective tissue growth factor (CTGF), secreted by endothelial cells, protects against acute liver injury, but its upstream mechanism is unclear. We aimed to clarify the protective role of CTGF in endothelial cell inflammation during IRI and reveal the regulation between endoplasmic reticulum stress-induced activating transcription factor 6 (ATF6) and CTGF. Hypoxia/reoxygenation in endothelial cells, hepatic IRI in mice and clinical specimens were used to examine the relationships between CTGF and inflammatory factors and determine how ATF6 regulates CTGF and reduces damage. We found that activating ATF6 promoted CTGF expression and reduced liver damage in hepatic IRI. In vitro, activated ATF6 upregulated CTGF and downregulated inflammation, while ATF6 inhibition had the opposite effect. Dual-luciferase assays and chromatin immunoprecipitation confirmed that activated ATF6 binds to the CTGF promoter, enhancing its expression. Activated ATF6 increases CTGF and reduces extracellular regulated protein kinase 1/2 (ERK1/2) phosphorylation, decreasing inflammatory factors. Conversely, inhibiting ATF6 decreases CTGF and increases the phosphorylation of ERK1/2, increasing inflammatory factor levels. ERK1/2 inhibition reverses this effect. Clinical samples have shown that CTGF increases after IRI, inversely correlating with inflammatory cytokines. Therefore, ATF6 activation during liver IRI enhances CTGF expression and reduces endothelial inflammation via ERK1/2 inhibition, providing a novel target for diagnosing and treating liver IRI.