Early Radiographic and Clinical Outcomes of Robotic-arm-assisted versus Conventional Total Knee Arthroplasty: A Multicenter Randomized Controlled Trial.

OBJECTIVE: A robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic-arm-assisted TKA improves clinical and radiological outcomes when compared to conventional TKA. METHODS: One hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow-up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full-length weight-bearing X-rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6-week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form-36 (SF-36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: At 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6-week postoperative functional outcomes, SF-36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be "positively related" to the robotic system. CONCLUSION: Robotic-arm-assisted TKA is safe and effective, as demonstrated in this trial.

PRRSV NSP1α degrades TRIM25 through proteasome system to inhibit host antiviral immune response.

Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant disease caused by porcine reproductive and respiratory syndrome virus (PRRSV). Type I interferon (IFN) induces a large number of interferon-stimulated genes (ISGs) expression to inhibit PRRSV infection. To survive in the host, PRRSV has evolved multiple strategies to antagonize host innate immune response. Previous studies have reported that PRRSV N protein decreases the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress IFN-ß production. However, whether other PRRSV proteins inhibit the antiviral function of TRIM25 is less well understood. In this study, we first found that PRRSV NSP1α decreased ISGylation of TRIM25. Meanwhile, NSP1α significantly suppressed TRIM25-mediated IFN-ß production to promote PRRSV replication. Further studies demonstrated that PRRSV NSP1α reduced the protein level of TRIM25 in proteasome system but did not regulate the transcription level of TRIM25. In addition, the function of NSP1α in TRIM25 degradation did not rely on its papain-like cysteine protease activity. Taken together, PRRSV NSP1α antagonizes the antiviral response of TRIM25 by mediating TRIM25 degradation to promote PRRSV replication. Our data identify TRIM25 as a natural target of PRRSV NSP1α and reveal a novel mechanism that PRRSV induces TRIM25 degradation and inhibits host antiviral immune response.

Clinical named entity recognition for percutaneous coronary intervention surgical information with hybrid neural network.

Percutaneous coronary intervention (PCI) has become a vital treatment approach for coronary artery disease, but the clinical data of PCI cannot be directly utilized due to its unstructured characteristics. The existing clinical named entity recognition (CNER) has been used to identify specific entities such as body parts, drugs, and diseases, but its specific potential in PCI clinical texts remains largely unexplored. How to effectively use CNER to deeply mine the information in the existing PCI clinical records is worth studying. In this paper, a total of 24 267 corpora are collected from the Cardiovascular Disease Treatment Center of the People's Hospital of Liaoning Province in China. We select three types of clinical record texts of fine-grained PCI surgical information, from which 5.8% of representative surgical records of PCI patients are selected as datasets for labeling. To fully utilize global information and multi-level semantic features, we design a novel character-level vector embedding method and further propose a new hybrid model based on it. Based on the classic Bidirectional Long Short-Term Memory Network (BiLSTM), the model further integrates Convolutional Neural Networks (CNNs) and Bidirectional Encoder Representations from Transformers (BERTs) for feature extraction and representation, and finally uses Conditional Random Field (CRF) for decoding and predicting label sequences. This hybrid model is referred to as BCC-BiLSTM in this paper. In order to verify the performance of the proposed hybrid model for extracting PCI surgical information, we simultaneously compare both representative traditional and intelligent methods. Under the same circumstances, compared with other intelligent methods, the BCC-BiLSTM proposed in this paper reduces the word vector dimension by 15%, and the F1 score reaches 86.2% in named entity recognition of PCI clinical texts, which is 26.4% higher than that of HMM. The improvement is 1.2% higher than BiLSTM + CRF and 0.7% higher than the most popular BERT + BiLSTM + CRF. Compared with the representative models, the hybrid model has better performance and can achieve optimal results faster in the model training process, so it has good clinical application prospects.

Super-resolution ultrasound and microvasculomics: a consensus statement.

This is a summary of a consensus statement on the introduction of "Ultrasound microvasculomics" produced by The Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The evaluation of microvessels is a very important part for the assessment of diseases. Super-resolution ultrasound (SRUS) microvascular imaging surpasses traditional ultrasound imaging in the morphological and functional analysis of microcirculation. SRUS microvascular imaging relies on contrast microbubbles to gain sensitivity to microvessels and improves the spatial resolution of ultrasound blood flow imaging for a more detailed depiction of vascular structures and hemodynamics. This method has been applied in preclinical animal models and pilot clinical studies, involving areas including neurology, oncology, nephrology, and cardiology. However, the current quantitative parameters of SRUS images are not enough for precise evaluation of microvessels. Therefore, by employing omics methods, more quantification indicators can be obtained, enabling a more precise and personalized assessment of microvascular status. Ultrasound microvasculomics - a high-throughput extraction of image features from SRUS images - is one novel approach that holds great promise but needs further validation in both bench and clinical settings. CLINICAL RELEVANCE STATEMENT: Super-resolution Ultrasound (SRUS) blood flow imaging improves spatial resolution. Ultrasound microvasculomics is possible to acquire high-throughput information of features from SRUS images. It provides more precise and abundant micro-blood flow information in clinical medicine. KEY POINTS: This consensus statement reviews the development and application of super-resolution ultrasound (SRUS). The shortcomings of the current quantification indicators of SRUS and strengths of the omics methodology are addressed. "Ultrasound microvasculomics" is introduced for a high-throughput extraction of image features from SRUS images.

Preparation of carboxymethyl chitosan/double-formaldehyde cellulose based hydrogel loaded with ginger essential oil nanoemulsion for meat preservation.

An antibacterial nano-hydrogel (ginger essential oil nanoemulsion hydrogel, GEONH) based on Schiff base reaction was prepared using double-formaldehyde micro fibrillated cellulose (DAMFC) and carboxymethyl chitosan (CMCS) loaded with ginger essential oil nanoemulsion (GEON). It was found that when the mass ratio of DAMFC/CMCS/GEON was 1/9/270, the gel time, the water absorbency, gel strength, and morphology were the best. The results of X-ray diffraction and FT-IR confirmed that the aldehyde group on the DAMFC molecular chain formed a stable chemical crosslinking with the amino group on the CMCS molecular chain, resulting in a change in the crystal structure. GEONH showed excellent bactericidal activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Simultaneously, the prepared GEONH decreased the total viable count, Malondialdehyde, and total sulfhydryl content and improved the taste in the storage of boiled salted duck. Therefore, GEONH film is a promising fresh-keeping packaging for storing meat products. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01437-4.

Differences in influencing mechanism of clinicians' adoption behavior for liver cancer screening technology between the leading and subordinate hospitals within medical consortiums.

BACKGROUND: Medical consortiums have been extensively established to facilitate the integration of health resources and bridge the technical gap among member institutions. However, some commonly appropriate technologies remain stagnant in subordinate hospitals, although they have been routinely applied in leading hospitals. Besides, the mechanism underlying differences in clinicians' adoption behavior at different levels of institutions was unknown. Therefore, this study aimed to investigate the differences in influencing mechanisms of clinicians' hepatic contrast-enhanced ultrasound technology (CEUS) utilization behavior between leading and subordinate hospitals within medical consortiums, thus providing clues for expanding effective and appropriate technologies within integrated care systems. METHODS: A self-designed scale was developed based on the theory of planned behavior (TPB). A multistage sampling method was applied to investigate clinicians who were aware of CEUS and worked in liver disease-related departments within the sampled medical institutions. The final sample size was 289. AMOS 24.0 software was used to construct multi-group structural equation modeling (SEM) to validate the hypotheses and determine the mechanism of hepatic CEUS utilization. RESULTS: It revealed that behavioral intention significantly influenced adoption behavior, regardless of whether it was in leading hospitals or subordinate hospitals (ß = 0.283, p < 0.001). Furthermore, behavioral attitude (ß = 0.361, p < 0.001) and perceived behavioral control (ß = 0.582, p < 0.001) exerted significant effects on adoption behavior through behavioral intention. However, in leading hospitals, subjective norm had a significant positive effect on behavioral intention (ß = 0.183, p < 0.01), while it had a significant negative impact on behavioral intention in the subordinate hospitals (ß = -0.348, p < 0.01). CONCLUSION: To effectively translate the adoption intention into actual behavior, it is recommended to elucidate the demand and facilitators involved in the process of health technology adoption across leading and subordinate hospitals. Additionally, bolstering technical support and knowledge dissemination within subordinate hospitals while harnessing the influential role of key individuals can further enhance this transformative process.

Adaptive Surface Normal Constraint for Geometric Estimation From Monocular Images.

We introduce a novel approach to learn geometries such as depth and surface normal from images while incorporating geometric context. The difficulty of reliably capturing geometric context in existing methods impedes their ability to accurately enforce the consistency between the different geometric properties, thereby leading to a bottleneck of geometric estimation quality. We therefore propose the Adaptive Surface Normal (ASN) constraint, a simple yet efficient method. Our approach extracts geometric context that encodes the geometric variations present in the input image and correlates depth estimation with geometric constraints. By dynamically determining reliable local geometry from randomly sampled candidates, we establish a surface normal constraint, where the validity of these candidates is evaluated using the geometric context. Furthermore, our normal estimation leverages the geometric context to prioritize regions that exhibit significant geometric variations, which makes the predicted normals accurately capture intricate and detailed geometric information. Through the integration of geometric context, our method unifies depth and surface normal estimations within a cohesive framework, which enables the generation of high-quality 3D geometry from images. We validate the superiority of our approach over state-of-the-art methods through extensive evaluations and comparisons on diverse indoor and outdoor datasets, showcasing its efficiency and robustness.

[Evaluation of early effectiveness of local infiltration anesthesia with compound betamethasone in total knee arthroplasty].

Objective: To evaluate the early effectiveness of local infiltration anesthesia (LIA) with compound betamethasone in total knee arthroplasty (TKA). Methods: The clinical data of 102 patients with knee osteoarthritis who were treated by TKA and met the selection criteria between May 2022 and March 2023 were retrospectively analyzed. They were divided into control group and study group according to whether LIA preparation was added with compound betamethasone, with 51 cases in each group. There was no significant difference of baseline data, such as age, gender, body mass index, operative side, preoperative range of motion (ROM), Knee Society Score (KSS), white blood cell (WBC), and hematocrit between the two groups ( P>0.05). The intraoperative total blood loss and hidden blood loss were recorded, and WBC was recorded on the 1st, 2nd, and 3rd days after operation. Pain was assessed by visual analogue scale (VAS) score on the 1st, 2nd, and 3rd days after operation and morphine intake milligrames equivalent within 48 hours after operation. Passive ROM, maximum extension and flexion angles of knee joint were measured on the 3rd day after operation; the early postoperative complications were recorded. Results: There was no significant difference in total blood loss and hidden blood loss between the two groups ( P>0.05). The postoperative pain levels in both groups were relatively mild, and there was no significant difference in VAS scores in the first 3 days after operation and in morphine intake milligrams equivalent within 48 hours after operation between the two groups ( P>0.05). The WBC in the first 3 days after operation was significantly improved in both groups ( P<0.05). The WBC in the study group was significantly higher than that in the control group on the 1st and 2nd days after operation ( P<0.05), but there was no significant difference between the two groups on the 3rd day after operation ( P>0.05). On the 3rd day after operation, the maximum extension angle of knee joint in the study group was smaller than that in the control group, while the maximum flexion angle and passive ROM of knee joint in the study group were larger than those in the control group, and the differences were significant ( P<0.05). There were 6 cases of fever and 17 cases of deep venous thrombosis in the control group, and 1 case and 14 cases in the study group, respectively. There was no poor wound healing and periprosthetic joint infection in the two groups, and there was no significant difference in the incidence of complications between the two groups ( P>0.05). Conclusion: The application of compound betamethasone in LIA during TKA is a safe and optimal strategy to promote the early postoperative rehabilitation of patients.

Trends in mortality of liver cancer in Wenzhou City from 2014 to 2022 / 预防医学

Objective@#To analyze the trends in mortality of liver cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for improving liver cancer control measures.@*Methods@#Data of liver cancer mortality in Wenzhou City from 2014 to 2022 were collected from Wenzhou Chronic Disease Monitoring Information System. The crude mortality were estimated and standardized by the national population census data in China in 2010, and the trends in mortality of liver cancer were analyzed with average annual percent change (AAPC).@*Results@#There were 22 033 liver cancer deaths from 2014 to 2022, accounting for 18.08% of malignant tumor deaths and ranking the second in malignant tumor deaths. The crude mortality of liver cancer was 30.00/105 and the standardized mortality was 24.32/105, both showing decreasing trends (AAPC=-2.812% and -5.742%, both P<0.05). The standardized mortality of liver cancer were higher in men than in women (36.66/105 vs. 11.21/105, P<0.05), both showing decreasing trends (AAPC=-5.702% and -5.521%, both P<0.05). The crude mortality of liver cancer appeared a tendency towards a rise with age (P<0.05), with the highest crude mortality in the group aged 80 to 84 years, reaching 145.12/105. The crude mortality of liver cancer showed a tendency towards a decline among residents aged under 15 years, 15 to 44 years, 45 to 64 years and 65 years and above (AAPC=-20.311%, -6.569%, -7.408% and -3.177%, all P<0.05).@*Conclusions@#The mortality of liver cancer showed a tendency towards a decline in Wenzhou City from 2014 to 2022. Men and the elderly were high-risk groups for liver cancer deaths, and prevention should be strengthened based on risk factors.

Appraising the role of the digital economy in global decarbonization: A spatial non-linear perspective on globalization.

In the context of globalization, the role of the digital economy in carbon emissions may generate spatial spill over effects. This study comprehensively applies a spatial model to understand the nexus between the digital economy and carbon emissions in 67 economies from 2010 to 2019. Specifically, this study contributes by introducing a spatial panel threshold model, which helps to present the new evidence regarding decarbonization process. Empirical findings exemplify that the digital economy remarkably reduces local carbon emissions, with the positive spatial spill over effects being salient. The spatial moderating effect model uncover that globalization positively affects the nexus between the digital economy and carbon emissions. Interestingly, the spatial panel threshold model designates that the digital economy's reduction effect on local carbon emissions will be tightened, whereas the positive spatial spill over effects turn negative only when globalization surpasses a threshold. Our model has the potential to explain some results that traditional models cannot reach.

A binary composite La(OH)3@Ni(OH)2 nanomaterial on carboxyl graphene for an efficient hybrid supercapacitor electrode.

In this work, we present a binary composite of La(OH)3@Ni(OH)2 on carboxyl graphene (La@Ni/CG) as an electrode material. The layered La@Ni/CG double hydroxides (LDHs) were synthesized by a simple electrodeposition method in which La(OH)3 nanoparticles were first adsorbed onto carboxyl graphene and then coated with Ni(OH)2, with different particle shapes due to the large pH change near the cathodic region. Scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) were used to characterise the as-prepared La@Ni/CG composite. These results showed that the La@Ni/CG composite exhibited improved electrochemical properties, including large specific capacitance (1334.7 F g-1 at 1.4 A g-1) and capacity retention of 90.6% even after 3000 cycles, and excellent rate capability. The improved electrochemical performance of the composite can be attributed to the synergistic effect of surface adsorption and conductive pathways provided by the multiple active species (Ni, La and C) in the La@Ni/CG composite. The results presented in this work provide advances in the efficient design of nanomaterial based electrochemical energy storage devices.

Evaporation kinetics during containerless chemical synthesis of ZIF-8 in levitated droplets.

Zeolitic imidazolate framework-8 was synthesized in a containerless state via acoustic levitation. The cavitation effect of ultrasound affected the coordination connection of organic ligands in acoustically levitated droplets and they exhibited a conspicuous difference in the particle size distribution as compared with those under normal conditions. Herein, methanol was chosen as the solvent to investigate the influence of droplet evaporation on acoustic levitation synthesis. The kinetic parameters of droplet evaporation such as geometrical morphology transformation, concentration change and temperature evolution were measured for the levitation state. Surface evaporation resulted in the drastic deformation of the droplet during ZIF-8 synthesis and caused its vertical vibration and shape oscillation. The abrupt change of the levitation state aggravated the sound field effect on the containerless synthesis and caused a decrease of particle size distribution. A two-dimensional axis-symmetry model was used to visually simulate the sound field distribution during acoustic levitation synthesis based on the finite element method. The fabricated ZIF-8 was able to remove phthalic acid in wastewater through adsorption, and its kinetic features followed a pseudo second-order rate model.

Counterfactual Samples Synthesizing and Training for Robust Visual Question Answering.

Today's VQA models still tend to capture superficial linguistic correlations in the training set and fail to generalize to the test set with different QA distributions. To reduce these language biases, recent VQA works introduce an auxiliary question-only model to regularize the training of targeted VQA model, and achieve dominating performance on diagnostic benchmarks for out-of-distribution testing. However, due to the complex model design, ensemble-based methods are unable to equip themselves with two indispensable characteristics of an ideal VQA model: 1) Visual-explainable: The model should rely on the right visual regions when making decisions. 2) Question-sensitive: The model should be sensitive to the linguistic variations in questions. To this end, we propose a novel model-agnostic Counterfactual Samples Synthesizing and Training (CSST) strategy. After training with CSST, VQA models are forced to focus on all critical objects and words, which significantly improves both visual-explainable and question-sensitive abilities. Specifically, CSST is composed of two parts: Counterfactual Samples Synthesizing (CSS) and Counterfactual Samples Training (CST). CSS generates counterfactual samples by carefully masking critical objects in images or words in questions and assigning pseudo ground-truth answers. CST not only trains the VQA models with both complementary samples to predict respective ground-truth answers, but also urges the VQA models to further distinguish the original samples and superficially similar counterfactual ones. To facilitate the CST training, we propose two variants of supervised contrastive loss for VQA, and design an effective positive and negative sample selection mechanism based on CSS. Extensive experiments have shown the effectiveness of CSST. Particularly, by building on top of model LMH+SAR (Clark et al. 2019), (Si et al. 2021), we achieve record-breaking performance on all out-of-distribution benchmarks (e.g., VQA-CP v2, VQA-CP v1, and GQA-OOD).

Novel PVA/carboxylated cellulose antimicrobial hydrogel grafted with curcumin and ε-polylysine for chilled chicken preservation.

PVA/CC/CUR/PL composite films containing curcumin (CUR) and ε-polylysine (PL) were prepared by casting and chemical grafting methods to address the threat to food spoilage. Morphological analysis showed that the grafting of CUR and PL resulted in a rough cross-section of the polymer matrix. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the grafting of CUR and PL into the polymer matrix via esterification and amidation reactions, respectively. Thermal weight loss analysis showed that grafting process positively improved the thermal stability. The PVA/CC/CUR/PL films exhibited strong bactericidal activity, reaching 99.0% and 99.8% for Pseudomonas lundensis and Shewanella putrefaciens, respectively. After 8 days of storage, the total number of colonies and the TVB-N content in the PVA/CC/CUR/PL group decreased by 1.51 lg CFU/g and 13.77 mg/100 g, respectively. Therefore, PVA/CC/CUR/PL films are considered as a promising bactericidal material with good mechanical properties, functionality, and other excellent characteristics.

[Progress of injection sites of local infiltration analgesia in total knee arthroplasty].

Objective: To review the research progress of injection sites of local infiltration analgesia (LIA) in total knee arthroplasty (TKA). Methods: The relevant domestic and foreign literature in recent years was extensively reviewed. The neuroanatomy of the knee, and the research progress of the selection and the difference of effectiveness between different injection sites of LIA in clinical studies were summarized. Results: Large concentrations of nociceptors are present throughout the various tissues of the knee joint. Patellar tendon, subpatellar fat pad, lateral collateral ligament insertions, iliotibial band insertions, suprapatellar capsule, and posterior capsule were more sensitive to pain. Most current studies support injections into the lateral capsule, collateral ligament, retinaculum, quadriceps tendon, fat pad, and subcutaneous tissue. Whether to inject into the back of the knee and subperiosteum is controversial. Conclusion: The relative difference of knee tissue sensitivity to pain has guiding significance for the selection of LIA injection site after TKA. Although researchers have conducted clinical trials on injection site and technique of LIA in TKA, there are certain limitations. The optimal scheme has not been determined yet, and further studies are needed.

Effects and Action Mechanism of Huoxue Tongluo Formula on the Formation of Neutrophil Extracellular Traps.

Excessive infiltration and uncontrolled activation of neutrophil extracellular traps (NETs) are likely to destroy normal tissue architecture and cause uncontrolled inflammation. The present research attempted to screen potential signaling pathways of Huoxue Tongluo Formula (HXTLF) affecting the formation of NETs using network pharmacology technique. Active chemical components of HXTLF and therapeutic targets related to vasculitis were screened, and a chemical components-targets network diagram of HXTLF was constructed by Cytoscape. Finally, the inhibitory effect and mechanism of HXTLF on the formation of NETs were explored in vitro using LPS-induced NETs. Immunofluorescence and Western blot were conducted to determine the protein fluorescence intensity and relative expression. The experimental results illustrated that HXTLF mediated the expression levels of H3Cit and myeloperoxidase (MPO) protein in neutrophils activated by LPS, inhibited NETs formation, and reduced the concentration of interleukin- (IL-) 1ß, a proinflammatory factor in cells. Additionally, we activated and inhibited the AKT1 signaling pathway using the corresponding activator and inhibitor to explore the regulatory mechanism of HXTLF on AKT1 and other molecules in the treatment of vasculitis. The results demonstrated that HXTLF could inhibit the phosphorylation of AKT1, IKK, and NF-κB proteins, inhibit NETs formation, and reduce IL-1ß concentration, indicating that AKT1 exerts a vital role in the treatment of vasculitis after HXTLF administration. The current study initially revealed the pharmacological mechanism of HXTLF for vasculitis management using network pharmacology techniques and tests in vitro, which is expected to provide important theoretical basis for elucidating the molecular mechanism of HXTLF and promoting its clinical application.

Floating synthesis with enhanced catalytic performance via acoustic levitation processing.

Acoustic levitation supplies a containerless state to eliminate natural convection and heterogeneous crystal nucleation and thus provides a highly uniform and ultra clean condition in the confined levitating area. Herein, we attempt to make full use of these advantages to fabricate well dispersed metal nanoparticles. The gold nanoparticles, synthesized in an acoustically levitated droplet, exhibited a smaller size and improved catalytic performance in 4-nitrophenol reduction were synthesized in an acoustically levitated droplet. The sound field was simulated to understand the impact of acoustic levitation on gold nanoparticle growth with the aid of crystal growth theory. Chemical reducing reactions in the acoustic levitated space trend to occur in a better dispersed state because the sound field supplies continuous vibration energy. The bubble movement and the cavitation effect accelerate the nucleation, decrease the size, and the internal flow inside levitated droplet probably inhibit the particle fusion in the growth stage. These factors lead to a reduction in particle size compared with the normal wet chemical synthetic condition. The resultant higher surface area and more numerous active catalytic sites contribute to the improvement of the catalytic performance.

NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression.

BACKGROUND: Dysregulation of the epitranscriptome causes abnormal expression of oncogenes in the tumorigenic process. Previous studies have shown that NAT10 can regulate mRNA translation efficiency through RNA acetylation. However, the role of NAT10-mediated acetylation modification in bladder cancer remains elusive. METHODS: The clinical value of NAT10 was estimated according to NAT10 expression pattern based on TCGA data set and the tumor tissue array. Acetylated RNA immunoprecipitation sequencing was utilized to explore the role of NAT10 in mRNA ac4C modification. Translation efficiency and mRNA stability assay were applied to study the effect of NAT10-deletion on target genes. The nude mouse model and genetically engineered mice were conducted to further verify the characteristics of NAT10 in promoting BLCA progression and regulating downstream targets. RESULTS: NAT10 was essential for the proliferation, migration, invasion, survival and the stem-cell-like properties of bladder cancer cell lines. NAT10 was responsible for mRNA ac4C modification in BLCA cells, including BCL9L, SOX4 and AKT1. Deficient NAT10 in both xenograft and transgenic mouse models of bladder cancer reduced the tumor burden. Furthermore, acetylated RNA immunoprecipitation sequencing data and RNA immunoprecipitation qPCR results revealed that NAT10 is responsible for a set of ac4C mRNA modifications in bladder cancer cells. Inhibition of NAT10 led to a loss of ac4C peaks in these transcripts and represses the mRNA's stability and protein expression. Mechanistically, the ac4C reduction modification in specific regions of mRNAs resulting from NAT10 downregulation impaired the translation efficiency of BCL9L, SOX4 and AKT1 as well as the stability of BCL9L, SOX4. CONCLUSIONS: In summary, these findings provide new insights into the dynamic characteristics of mRNA's post-transcriptional modification via NAT10-dependent acetylation and predict a role for NAT10 as a therapeutic target in bladder cancer. HIGHLIGHTS: NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumourigenic properties. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1. NAT10 may serve as an effective and novel therapeutic target for BLCA.

Predictors of physicians' intentions to use clinical practice guidelines on antimicrobial in tertiary general hospitals of China: a structural equation modeling approach.

BACKGROUND: With inappropriate use of antimicrobials becoming a great public health concern globally, the issue of applying clinical practice guidelines (CPGs) to regulate the rational use of antimicrobials has attracted increasing attention. Taking tertiary general hospitals in China for example, this study aimed to identify factors to investigate the comprehensive influencing mechanism for physicians' intention to use CPGs on antimicrobials. METHODS: Based on the integration of Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), and Technology-Organization-Environment framework (TOE), a questionnaire survey was conducted covering potential determinants of affecting physicians' intentions to use CPGs on antimicrobials at the individual level (attitude, subjective norms and perceived risk), technical level (relative advantage and ease of use), and organizational level (top management support and organizational implementation). Data were collected from 644 physicians in tertiary general hospitals in eastern, central and western China, which were obtained by multi-stage random sampling. The structural equation modeling (SEM) was used to link three-level factors with physicians' behavioral intentions. RESULTS: The majority of the participants (94.57%) showed a positive tendency toward intention to use CPGs on antimicrobials. The reliability and validity analysis showed the questionnaire developed from the theoretical model was acceptable. SEM results revealed physicians' intentions to use CPGs on antimicrobials was associated with attitude (ß = 0.166, p < 0.05), subjective norms (ß = 0.244, p < 0.05), perceived risk (ß = - 0.113, p < 0.05), relative advantage (ß = 0.307, p < 0.01), top management support (ß = 0.200, p < 0.05) and organizational implementation (ß = 0.176, p < 0.05). Besides, subjective norms, perceived risk, relative advantage, ease of use, and top management support showed their mediating effects from large to small on the intentions, which were 0.215, 0.140, 0.103, 0.088, - 0.020, respectively. CONCLUSIONS: This study revealed the significance of multifaceted factors to enhance the intention to use CPGs on antimicrobials. These findings will not only contribute to the development of targeted intervention strategies on promoting the use of CPGs on antimicrobials, but also provide insights for future studies about physicians' adoption behaviors on certain health services or products.

What factors predict physicians' utilization behavior of contrast-enhanced ultrasound? Evidence from the integration of the Theory of Planned Behavior and Technology Acceptance Model using a structural equation modeling approach.

BACKGROUND: The promotion of early diagnosis is undoubtedly effective in reducing the burden of disease. Contrast-enhanced ultrasound (CEUS) is a diagnostic technology for liver cancer, but its implementation faces some challenges. Understanding the influencing factors of CEUS utilization is crucial for its successful implementation. However, such research is rare. The aims of this study were to investigate the status of CEUS utilization and its predictors in China. METHODS: Through multistage random sampling, a cross-sectional study design was conducted among physicians in charge of direct use of CEUS working at liver disease-related departments of sampled health institutions. To access the potential influencing factors of physicians' CEUS utilization, a structured questionnaire was developed based on the theoretical model, which was developed by integration of the Theory of Planned Behavior (TPB) and Technology Acceptance Model (TAM). Structural equation modeling was used to verify the proposed hypotheses, and analyze the relationship and mechanism between the factors. RESULTS: A total of 309 physicians were enrolled. The mean score of utilization behavior was 2.04 (SD = 1.07), and 37.22% above the mean. The favorable fitting results demonstrated that the integration of TAM and TPB was an acceptable model. SEM results also identified physicians' intentions to use CEUS was directly associated with utilization behavior (ß = 0.287, P < 0.001). Attitude (ß = 0.272, P < 0.001), subjective norm (ß = 0.172, P = 0.013), perceived behavioral control (ß = 0.491, P < 0.001) and perceived usefulness (ß = 0.108, P = 0.027) significantly influenced physicians' intentions. Besides, subjective norm (ß = 0.065, P = 0.021), perceived behavioral control (ß = 0.141, P = 0.003), and perceived ease of use (ß = 0.022, P = 0.033) indirectly affected physicians' CEUS utilization. CONCLUSIONS: The findings provide a reference for understanding the factors associated with physicians' utilization of CEUS. Additionally, the proposed measures such as building innovative and incentive environment, providing high quality and adequate training, etc., will help promote the utilization of CEUS, thereby increasing the detection rate of liver cancer, and improving the survival rate and the quality of life for liver cancer patients.