Antibiotic resistance at environmental multi-media interfaces through integrated genotype and phenotype analysis.

Antibiotic resistance is currently an unfolding global crisis threatening human health worldwide. While antibiotic resistance genes (ARGs) are known to be pervasive in environmental media, the occurrence of antibiotic resistance at interfaces between two or more adjacent media is largely unknown. Here, we designed a microcosm study to simulate plastic pollution in paddy soil and used a novel method, stimulated Raman scattering coupled with deuterium oxide (D2O) labelling, to compare the antibiotic resistance in a single medium with that at the interface of multiple environmental media (plastic, soil, water). Results revealed that the involvement of more types of environmental media at interfaces led to a higher proportion of active resistant bacteria. Genotypic analysis showed that ARGs (especially high-risk ARGs) and mobile genetic elements (MGEs) were all highly enriched at the interfaces. This enrichment was further enhanced by the co-stress of heavy metal (arsenic) and antibiotic (ciprofloxacin). Our study is the first to apply stimulated Raman scattering to elucidate antibiotic resistance at environmental interfaces and reveals novel pathway of antibiotic resistance dissemination in the environment and overlooked risks to human health.

Facile Fabrication of Co-Doped Porous Carbon from Coal Hydrogasification Semi-Coke for Efficient Microwave Absorption.

A Co-doped porous carbon was successfully fabricated by a facile carbonizing procedure using coal hydrogasification semi-coke (SC) as the carbon and cobalt nitrate as the magnetic precursors, respectively. The mass ratio of the precursors was changed to regulate the microwave absorption (MA) capabilities. The favorable MA capabilities are a result of a synergistic interaction be-tween the dielectric loss from the carbon framework, the magnetic loss from nano-sized Co particles, and multiple scattering from the residual pores. At a thickness of 4.0 mm, the Co/C composite showed the lowest reflection loss of -33.45 dB when the initial mass ratio of cobalt nitrate and SC was 1:1. The effective absorbing bandwidth (EAB) could achieve 3.5 GHz at 2 mm thickness. This work not only opens up a new avenue for the facile fabrication of dielectric and magnetic loss combinations and their structural design, but it also creates a new route for the high value-added exploitation of SC.

[A retrospective study on two different surgical robots to assist total knee arthroplasty].

OBJECTIVE: To compare early clinical and imaging results of domestic HURWA and imported Brainlab Knee3 surgical robot-assisted knee replacement. METHODS: A retrospective analysis was performed on 93 patients with knee osteoarthritis (KOA) who underwent robot-assisted descending total knee arthroplasty(TKA) from January 2021 to July 2023, and they were divided into BRATKA group and HRATKA group according to use of robotic system. There were 40 patients in BRATKA group, including 16 males and 24 females, aged from 55 to 90 years old with an average of (64.3±7.0) years old;27 patients with grade Ⅲ and 13 patients with grade Ⅳ according to Kellgren-Lawrence(K-L);18 patients on the right side and 22 patients on the left side;the courses of disease ranged from 1 to 30 years with an average of (15.3±7.6) years;imported Brainlab Knee3 surgical robot assisted system was adopted. There were 53 patients in HRATKA group, including 18 males and 35 females, aged from 52 to 81 years old with an average of (64.4±8.5) years old;30 patients with grade Ⅲ and 23 patients with grade Ⅳ;21 patients on the right side and 32 patients on the left side;the courses of disease ranged from 1 to 32 years with an average of (16.4±7.9) years;HURWA surgical robot assisted system was adopted. Operation time, perioperative total blood loss, incision length and postoperative complications were compared between two groups. Deviation angle of hip-knee-ankle angle(HKAA) before operation and on the first day after operation was compared between two groups. Later tibal component (LTC), frontal femoral component (FFC), later femoral component (LFC) and frontal tibal component(FTC) at 1 day after on the first day after operation was compared between two groups. Knee Society score(KSS), visual analogue scale (VAS) and range of motion (ROM) of knee joint were compared between two groups before operation and on the 3rd and 90th day after operation. RESULTS: Both groups were followed up for 11 to 18 months with an average of (14.4±2.1) months, and the wounds of all patients healed well. Operation time and incision length of BRATKA group were (132.1±34.6) min and (12.9±1.9) cm, while (94.1±10.8) min and (14.8±2.1) cm in HRATKA group, respectively, and the differences between two groups were statistically significant(P<0.05). There were no significant difference in perioperative total blood loss and preoperative deviation angle of HKAA between two groups(P>0.05). Deviation angle of HKAA, FFC angle and LFC angle in BRATKA group were (1.90±0.91) °, (87.90±1.51) ° and(9.00±3.2) °, respectively;while (0.93±1.04) °, (89.03±0.96) ° and (7.63±0.59) ° in HRATKA group, respectively, and the differences between two groups were statistically significant (P<0.05). There were no significant differences in FTC and LTC between two groups(P>0.05). There were no significant differences in VAS of knee rest and exercise, KSS score and ROM of knee joint between two groups before operation and 3 days and 90 days after operation(P>0.05). There was no significant difference in complications between two groups (P>0.05). CONCLUSION: Postoperative imaging of two robot systems showed good lower limb force line. The domestic HRATKA group had better LFC, FFC angle and HKA deviation angle than the imported BRATKA group, but there were no significant difference in postoperative knee function and pain relief.

Veno-venous extracorporeal membrane oxygenation-assisted treatment of severe airway stenosis due to goiter: Two case reports.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) is a critical care intervention that acts as a temporary substitute for the heart and lungs, facilitating adequate tissue perfusion and gas exchange. The 2 primary configurations, veno-arterial and veno-venous ECMO, are tailored to support either the heart and lungs or the lungs alone, respectively. PATIENT CONCERNS: The case report details patients with tumor-induced airway stenosis who encountered limitations with standard treatments, which were either insufficient or carried the risk of severe complications such as hypoxia and asphyxia. DIAGNOSES: Patients were diagnosed with severe airway stenosis caused by goiter, a condition that required innovative treatment approaches to prevent complications during the management process. INTERVENTIONS: Veno-venous ECMO was implemented as a bridging therapy to provide vital respiratory support during the tumor resection procedure. This intervention was crucial in reducing the risks associated with airway edema or tumor rupture. OUTCOMES: With the use of veno-venous ECMO, the patients successfully underwent tumor resection. They were subsequently weaned off the ECMO support, and after a course of treatment, they were discharged in good condition. LESSONS: The case demonstrates the efficacy of veno-venous ECMO as a bridging therapy for managing severe airway stenosis caused by goiter. Its use facilitated the successful resection of tumors and led to positive patient outcomes, highlighting its potential as a valuable treatment option in similar scenarios.

Evaluating the reduction of elective radiotherapy fields for de novo metastatic nasopharyngeal carcinoma in the immunotherapy era.

BACKGROUND: This study evaluates the outcomes of omitting the high- and low-risk clinical tumor volume (CTV1 and CTV2) radiation in de novo metastatic nasopharyngeal carcinoma (dnm-NPC) patients in the immunotherapy era. METHODS: We retrospectively analyzed 45 consecutive dnm-NPC patients receiving chemotherapy and immunotherapy combined with radiotherapy (CIR) from October 9, 2018 to June 1, 2022. Irradiation was only delivered to the primary tumor and retropharyngeal nodes (GTVnx+rn) and gross cervical lymph nodes (GTVnd). RESULTS: The median follow-up was 45 (range, 15-67) months. There was no recurrence in the omitted elective regions. The 36-month LRRFS, PFS, and OS were 95.4%, 44.6%, and 90.8%, respectively. The main grade 3/4 hematologic toxicities were neutropenia (42.2%), anemia (20.0%), and thrombocytopenia (13.3%). The incidence of acute grade 3/4 dermatitis, mucositis, and xerostomia were 4.4%, 8.9%, and 4.4%, respectively. CONCLUSIONS: Omitting CTV1 and CTV2 was well-tolerated and provided favorable clinical outcomes in the era of immunotherapy.

Efficient production of phenyllactic acid in Escherichia coli via metabolic engineering and fermentation optimization strategies.

Phenyllactic acid (PhLA), an important natural organic acid, can be used as a biopreservative, monomer of the novel polymeric material poly (phenyllactic acid), and raw material for various medicines. Herein, we achieved a high-level production of PhLA in Escherichia coli through the application of metabolic engineering and fermentation optimization strategies. First, the PhLA biosynthetic pathway was established in E. coli CGSC4510, and the phenylalanine biosynthetic pathway was disrupted to improve the carbon flux toward PhLA biosynthesis. Then, we increased the copy number of the key genes involved in the synthesis of the PhLA precursor phenylpyruvic acid. Concurrently, we disrupted the tryptophan biosynthetic pathway and enhanced the availability of phosphoenolpyruvate and erythrose 4-phosphate, thereby constructing the genetically engineered strain MG-P10. This strain was capable of producing 1.42 ± 0.02 g/L PhLA through shake flask fermentation. Furthermore, after optimizing the dissolved oxygen feedback feeding process and other conditions, the PhLA yield reached 52.89 ± 0.25 g/L in a 6 L fermenter. This study successfully utilized metabolic engineering and fermentation optimization strategies to lay a foundation for efficient PhLA production in E. coli as an industrial application.

Comparative Study of Preoperative Sagittal Spinal Pelvic Alignment in Patients with Cervical Spondylotic Radiculopathy, Ossification of the Posterior Longitudinal Ligament, and Cervical Spondylotic Myelopathy.

OBJECTIVES: Cervical spondylosis may lead to changes in the sagittal parameters of the neck and trigger compensatory alterations in systemic sagittal parameters. However, there is currently a dearth of comparative research on the changes and compensatory alterations to sagittal parameters resulting from different types of cervical spondylosis. This study compared the preoperative sagittal alignment sequences among patients with cervical spondylotic radiculopathy (CSR), ossification of the posterior longitudinal ligament (OPLL), and cervical spondylotic myelopathy (CSM) caused by factors resulting from non-OPLL factors. MATERIALS AND METHODS: Full length lateral X-ray of the spine and cervical computed tomography (CT) of 256 patients (134 men, 122 women; mean age, 56.9 ± 9.5 years) were analyzed retrospectively. A total of 4096 radiomics features were measured through the lateral X-ray by two spinal surgeons with extensive experience. The clinical symptoms measures were the Japanese Orthopaedic Association (JOA) score, number of hand actions in 10 s, hand-grip strength, visual analog scale (VAS) score. Normally distributed data was compared using one-way analysis of variance (ANOVA) for parametric variables and χ2 test were used to analyze the categorical data. RESULTS: In the OPLL group, the C2-C7 Cobb angle was greater than in the CSR and CSM groups (19.8 ± 10.4°, 13.3 ± 10.3°, and 13.9 ± 9.9°, respectively, p < 0.001). Additionally, the C7-S1 SVA measure was found to be situated in the anterior portion with regards to the CSM and CSR groups (19.7 ± 58.4°, -6.3 ± 34.3° and -26.3 ± 32.9°, p < 0.001). Moreover, the number of individuals with C7-S1 SVA >50 mm was significantly larger than the CSM group (26/69, 11/83, p < 0.001). In the CSR group, the TPA demonstrated smaller values compared to the OPLL group (8.8 ± 8.5°, 12.7 ± 10.2°, p < 0.001). Furthermore, the SSA was comparatively smaller as opposed to both the OPLL and CSM groups (49.6 ± 11.2°, 54.2 ± 10.8° and 54.3 ± 9.3°, p < 0.05). CONCLUSION: Patients with OPLL exhibit greater cervical lordosis than those with CSR and CSM. However, OPLL is more likely to result in spinal imbalance when compared to the CSM group. Furthermore, OPLL and CSM patients exhibit anterior trunk inclination and worse global spine sagittal parameters in comparison to CSR patients.

Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis.

Purpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.

Spatial Pattern of Host Tree Size, Rather than of Host Tree Itself, Affects the Infection Likelihood of a Fungal Stem Disease.

The spatial pattern of diseased forest trees is a product of the spatial pattern of host trees and the disease itself. Previous studies have focused on describing the spatial pattern of diseased host trees, and it remains largely unknown whether an antecedent spatial pattern of host/nonhost trees affects the infection pattern of a disease and how large the effect sizes of the spatial pattern of host/nonhost trees and host size are. The results from trivariate random labeling showed that the antecedent pattern of the host ash tree, Fraxinus mandshurica, but not of nonhost tree species, impacted the infection pattern of a stem fungal disease caused by Inonotus hispidus. To investigate the effect size of the spatial pattern of ash trees, we employed the SADIE (Spatial Analysis by Distance IndicEs) aggregation index and clustering index as predictors in the GLMs. Globally, the spatial pattern (vi index) of ash trees did not affect the infection likelihood of the focal tree; however, the spatial pattern of DBH (diameter at breast height) of ash trees significantly affected the infection likelihood of the focal tree. We sampled a series of circular plots with different radii to investigate the spatial pattern effect of host size on the infection likelihood of the focal tree locally. The results showed that the location (patch/gap) of the DBH of the focal tree, rather than that of the focal tree itself, significantly affected its infection likelihood in most plots of the investigated sizes. A meta-analysis was employed to settle the discrepancy between plots of different sizes, which led to results consistent with those of global studies. The results from meta-regression showed that plot size had no significant effects.

WFB: watermarking-based copyright protection framework for federated learning model via blockchain.

Federated learning (FL) enables users to train the global model cooperatively without exposing their private data across the engaged parties, which is widely used in privacy-sensitive business. However, during the life cycle of FL models, both adversaries' attacks and ownership generalization threaten the FL models' copyright and affect the models' reliability. To address these problems, existing model watermarking techniques can be used to verify FL model's ownership. However, due to the lack of credible binding from "model extracted watermarks" to "ownership verification", it is difficult to form a closed-loop watermarking framework for copyright protection. Therefore, starting from the shortcomings of the current watermark verification scheme, this article proposed WFB, a blockchain-empowered watermarking framework for ownership verification of federated models. Firstly, we propose a improved watermark generation algorithm to solve the credibility issue of watermarks. Secondly, we propose a watermark embedding method in federated learning, while blockchain technology is used to ensure the credible storage of watermark information throughout the process. Thirdly, the credibility of ownership verification is improved because of the watermark authenticity. Experimental results demonstrate the fidelity, effectiveness and robustness of WFB, with other superiorities such as improving process security and traceability.

Latent profiles of narrative competence and professional identity among nursing students: A cross-sectional analytic study based on the Ring theory of personhood.

AIM: To identify latent profiles of narrative competence in nursing students and examine the association between the potential competence profiles and professional identity from a person-centred perspective. BACKGROUND: According to the Ring theory of personhood, nursing students can develop their professional identities from individual, relational and social aspects through interaction with patients, as well as listening to, understanding and responding to patients' disease narratives. However, few studies have examined the relationship between narrative competence and professional identity through the quantitative method. DESIGN: A cross-sectional analytic study. METHODS: A total of 472 nursing students responded to the survey between March and May 2023. The Professional Identity Questionnaire for Nurse Students and the Narrative Competence Scale were given to participants. Latent profile analysis was conducted to identify narrative competence profiles. The Bolck-Croon-Hagenaars method was used to analyse whether these latent profiles for narrative competence affected nursing students' general, individual, interpersonal and social professional identities. RESULTS: Latent profiles were identified as "low narrative competence" (12.1 %), "relatively low narrative competence" (39.9 %), "moderate narrative competence" (40.1 %) and "high narrative competence" (7.9 %). The profiles only show level differences rather than combinations of competence areas. These profiles had varying effects on the nursing students' general professional identities, as well as their individual, relational and social professional identities. CONCLUSION: This study highlights the significance of providing tailored guidance and support to nursing students, taking into account their unique narrative competency profile, to promote the formation of professional identity from individual, relational and social aspects. Nursing educators should effectively distinguish nursing students with inadequate narrative competence and value patients' disease narratives to promote narrative competence and professional identity.

Integration of machine learning XGBoost and SHAP models for NBA game outcome prediction and quantitative analysis methodology.

This study investigated the application of artificial intelligence in real-time prediction of professional basketball games, identifying the variations within performance indicators that are critical in determining the outcomes of the games. Utilizing games data from the NBA seasons 2021 to 2023 as the sample, the study constructed a real-time predictive model for NBA game outcomes, integrating the machine learning XGBoost and SHAP algorithms. The model simulated the prediction of game outcomes at different time of games and effectively quantified the analysis of key factors that influenced game outcomes. The study's results demonstrated that the XGBoost algorithm was highly effective in predicting NBA game outcomes. Key performance indicators such as field goal percentage, defensive rebounds, and turnovers were consistently related to the outcomes at all times during the game. In the first half of the game, assists were a key indicator affecting the outcome of the game. In the second half of the games, offensive rebounds and three-point shooting percentage were key indicators affecting the outcome of the games. The performance of the real-time prediction model for NBA game outcomes, which integrates machine learning XGBoost and SHAP algorithms, is found to be excellent and highly interpretable. By quantifying the factors that determine victory, it is able to provide significant decision support for coaches in arranging tactical strategies on the court. Moreover, the study provides reliable data references for sports bettors, athletes, club managers, and sponsors.

Platelet-derived Growth Factor Receptor-α Induces Contraction Knots and Inflammatory Pain-like Behavior in a Rat Model of Myofascial Trigger Points.

BACKGROUND: Myofascial trigger points (MTrPs) are the primary etiological characteristics of chronic myofascial pain syndrome. Receptor tyrosine kinases (RTKs) are associated with signal transduction in the central mechanisms of chronic pain, but the role of RTKs in the peripheral mechanisms of MTrPs remains unclear. The current study aimed to identify RTKs expression in MTrPs and elucidate the molecular mechanisms through which platelet-derived growth factor receptor-α (PDGFR-α) induces contraction knots and inflammatory pain-like behavior in a rat model of myofascial trigger points. METHODS: MTrPs tissue samples were obtained from the trapezius muscles of patients with myofascial pain syndrome through needle biopsy, and PDGFR-α activation was analyzed by microarray, enzyme-linked immunosorbent assay, and histological staining. Sprague-Dawley rats (male and female) were used to investigate PDGFR-α signaling, assessing pain-like behaviors with Randall-Selitto and nest-building tests. Muscle fiber and sarcomere morphologies were observed using histology and electron microscopy. The PDGFR-α binding protein was identified by coimmunoprecipitation, liquid chromatograph mass spectrometer, and molecular docking. PDGFR-α-related protein or gene levels, muscle contraction, and inflammatory markers were determined by Western blot and reverse-transcription quantitative polymerase chain reaction. RESULTS: PDGFR-α phosphorylation levels were elevated in the MTrPs tissues of individuals with trapezius muscle pain and were positively correlated with pain intensity. In rats, PDGFR-α activation caused pain-like behaviors and muscle contraction via the Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathway. JAK2/STAT3 inhibitors reversed the pain-like behaviors and muscle contraction induced by PDGFR-α activation. Collagen type I α 1 (COL1A1) binds to PDGFR-α and promotes its phosphorylation, which contributed to pain-like behaviors and muscle contraction. CONCLUSIONS: COL1A1-induced phosphorylation of PDGFR-α and the subsequent activation of the JAK2/STAT3 pathway may induce dysfunctional muscle contraction and increased nociception at MTrPs.

Bioinformatics prediction and experimental verification identify a cuproptosis-related gene signature as prognosis biomarkers of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) of which its prognostic prediction is still unclarified is a highly heterogeneous disease. Cuproptosis is a form of cell death that depends on copper regulation. Whether the cuproptosis-related genes can be the prognostic indicators of HCC is yet to be elucidated. The aim of this study is to investigate whether cuproptosis-related genes play a role in HCC and can be used as a diagnostic index to predict the occurrence of liver cancer. Methods: We downloaded HCC patients' gene expression profiles and their corresponding clinical data from a public database. To screen data, we used single factor Cox regression analysis, meanwhile, polymerase chain reaction (PCR) was used for the verification. After that, the risk score was calculated and the relationship between risk score and clinical factors was analyzed. Besides, a nomogram map was constructed for predicting the prognosis of HCC, and calibration map and decision curve analysis (DCA) map were used to test the model. Results: Compared to the high expression group of four cuproptosis-related genes, the low expression group showed better overall survival (OS) [hazard ratio (HR) =2.58; 95% confidence interval (CI): 1.72-3.89, P<0.01]. The expression of the four cuproptosis-relate genes increased in liver cancer cell lines compared to liver cell lines (P<0.05). Based on these four genes, we calculated the risk score and divided them into two groups as high-risk group and low-risk group. The risk factor map showed the high-risk group had shorter survival time and the four genes were highly expressed. The area under curve (AUC) of receiver operating characteristic (ROC) prediction curve for the first year was 0.726. Risk scores were closely related to clinical factors and immune cells. Finally, we constructed a nomogram for predicting the prognosis of HCC. Conclusions: The risk score for cuproptosis-related genes was established and involved in the construction of the nomogram, providing a new perspective on the prognosis and copper metabolism of HCC.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

Synergistic immunochemotherapy targeted SAMD4B-APOA2-PD-L1 axis potentiates antitumor immunity in hepatocellular carcinoma.

Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-'O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC. Here, we propose for the first time a synergistic immunochemotherapy that exerts a potent antitumour effect for patients with advanced hepatocellular carcinoma (HCC) in clinical practice based on three common antitumour drugs and found that HCC patients with new synergistic immunochemotherapy had better three-year overall survival (p = 0.004) and significantly higher survival ratio (increased by 2.3 times) than the control group. We further reveal the immunoregulatory mechanism of synergistic immunochemotherapy through 2'-O-Methylation modification mediated by SAMD4B, a tumour suppressor gene. Mechanistically, SAMD4B, increased by the reduced mutations of upstream genes NOTCH1 and NOTCH2, affected the instability of APOA2 mRNA by 2-'O-Methylation modification of the C-terminus. The decreased APOA2 further attenuated programmed death ligand 1 (PD-L1) level with a direct interaction pattern. The high-SAMD4B tumour tissues contained fewer native CD29+CD8+ T cells, which improved immune microenvironment to achieve the effect of antitumour effect. Overall, we developed a potent synergistic immunochemotherapy strategy that exerts an efficient anti-HCC effect inducing SAMD4B-APOA2-PD-L1 axis to inhibit tumour immune evasion.

Sirolimus-eluting iron bioresorbable scaffold versus cobalt-chromium everolimus-eluting stents in patients with coronary artery disease: Rationale and design of the IRONMAN-II trial.

BACKGROUND: The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). METHODS: A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). CONCLUSION: This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds.