Targeting treatment resistance: unveiling the potential of RNA methylation regulators and TG-101,209 in pan-cancer neoadjuvant therapy.

BACKGROUND: Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy. METHODS: Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification. RESULTS: Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy. CONCLUSIONS: This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.

Facet-Controlled Synthesis of Unconventional-Phase Metal Alloys for Highly Efficient Hydrogen Oxidation.

Facet control and phase engineering of metal nanomaterials are both important strategies to regulate their physicochemical properties and improve their applications. However, it is still a challenge to tune the exposed facets of metal nanomaterials with unconventional crystal phases, hindering the exploration of the facet effects on their properties and functions. In this work, by using Pd nanoparticles with unconventional hexagonal close-packed (hcp, 2H type) phase, referred to as 2H-Pd, as seeds, a selective epitaxial growth method is developed to tune the predominant growth directions of secondary materials on 2H-Pd, forming Pd@NiRh nanoplates (NPLs) and nanorods (NRs) with 2H phase, referred to as 2H-Pd@2H-NiRh NPLs and NRs, respectively. The 2H-Pd@2H-NiRh NRs expose more (100)h and (101)h facets on the 2H-NiRh shells compared to the 2H-Pd@2H-NiRh NPLs. Impressively, when used as electrocatalysts toward hydrogen oxidation reaction (HOR), the 2H-Pd@2H-NiRh NRs show superior activity compared to the NiRh alloy with conventional face-centered cubic (fcc) phase (fcc-NiRh) and the 2H-Pd@2H-NiRh NPLs, revealing the crucial role of facet control in enhancing the catalytic performance of unconventional-phase metal nanomaterials. Density functional theory (DFT) calculations further unravel that the excellent HOR activity of 2H-Pd@2H-NiRh NRs can be attributed to the more exposed (100)h and (101)h facets on the 2H-NiRh shells, which possess high electron transfer efficiency, optimized H* binding energy, enhanced OH* binding energy, and a low energy barrier for the rate-determining step during the HOR process.

Bidirectional, longitudinal associations between depressive symptoms and IADL/ADL disability in older adults in China: a national cohort study.

INTRODUCTION: Based on the data from the China Health and Retirement longitudinal study (CHARLS), we aimed to investigate the bidirectional relationship between depressive symptoms and functional disability. METHODS: Data were collected across 3 waves from 2013 to 2018. The activities of daily living (ADLs) and the instrumental activities of daily living (IADLs) scales were used to measure functional disability and the CESD-10 was used to measure depressive symptoms. Cross-lagged models were performed to examine cross effect between depressive symptoms and functional disability across three waves. RESULTS: Data on 10,092(mean [SD] age, 61.98[8.44] years; 3764 females [37.30%]) and 10,180 participants (mean [SD] age, 62.01[8.46] years; 3788 females [37.21%]) in IADL sample and ADL sample were included in the analyses. For IADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes in CESD-10 score across waves were associated with worse IADL disability (ß ranges: 0.08-0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (ß ranges: 0.09-0.10). For ADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes of CESD-10 score across waves were associated with worse IADL disability (ß ranges: 0.08-0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (ß ranges: 0.09-0.10). DISCUSSION: Study findings underscore a significant bidirectional between depressive symptoms and functional disability in older adults. Thus, simultaneous intervention should be taken to manage the mutual development of functional disability and depression.

[Whole Process Analysis and Fate Behavior of Microplastics in Urban Wastewater Treatment Plants, Including their Occurrence Forms, Components, and Removal Efficiency].

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that： fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance； the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances （PET, PBT）, cellulose, and polypropylene （PP） were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was （73 ±5） n·L-1, the effluent abundance was （14 ±2） n·L-1, and the overall removal rate was （80.8 ±12.1）%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids （49.2 ±7.4）% and secondary sedimentation tanks （92.4 ±13.9）%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.

Analyzing Spatio-Temporal Dynamics of Grassland Resilience and Influencing Factors in the West Songnen Plain, China, for Eco-Restoration.

Grassland plays an indispensable role in the stability and development of terrestrial ecosystems. Quantitatively assessing grassland resilience is of great significance for conducting research on grassland ecosystems. However, the quantitative measurement of resilience is difficult, and research on the spatio-temporal variation of grassland resilience remains incomplete. Utilizing the Global Land Surface Satellite (GLASS) leaf area index (LAI) product derived from MODIS remote sensing data, along with land cover and meteorological data, this paper constructed the grassland resilience index (GRI) in the west Songnen Plain, China, a typical region with salt and alkali soils. This paper analyzed the spatio-temporal changes of the GRI and explored the contribution of climate factors, human activities, and geographical factors to the GRI. The results revealed that from 2000 to 2021, the GRI in the study area ranged from 0.1 to 0.22, with a multi-year average of 0.14. The average GRI exhibited a pattern of high-value aggregations in the north and low-value distributions in the south. Trend analysis indicated that areas with an improved GRI accounted for 59.09% of the total grassland area, but there were still some areas with serious degradation. From 2000 to 2015, the latitude and mean annual temperature (MAT) were principal factors to control the distribution of the GRI. In 2020, the mean annual precipitation (MAP) and MAT played important roles in the distribution of the GRI. From 2000 to 2021, the influence of human activities was consistently less significant compared to geographical location and climate variables.

Effects of antibiotic cocktail on the fecal microbiota and their potential correlation of local immune response.

BACKGROUND: The guts of mammals are home to trillions of microbes, forming a complex and dynamic ecosystem. Gut microbiota is an important biological barrier for maintaining immune homeostasis. Recently, the use of antibiotics to clear gut microbiota has gained popularity as a low cost and easy-to-use alternative to germ-free animals. However, the effect of the duration of the antibiotic cocktail on the gut microbiome is unclear, and more importantly, the effect of dramatic changes in the gut microbiota on intestinal tissue morphology and local immune response is rarely reported. RESULTS: We observed a significant reduction in fecal microbiota species and abundance after 1 week of exposure to an antibiotic cocktail, gavage twice daily by intragastric administration. In terms of composition, Bacteroidetes and Firmicutes were replaced by Proteobacteria. Extending antibiotic exposure to 2-3 weeks did not significantly improve the overall efficiency of microbiotal consumption. No significant histomorphological changes were observed in the first 2 weeks of antibiotic cocktail exposure, but the expression of inflammatory mediators in intestinal tissue was increased after 3 weeks of antibiotic cocktail exposure. Mendelian randomization analysis showed that Actinobacteria had a significant causal association with the increase of IL-1ß (OR = 1.65, 95% CI = 1.23 to 2.21, P = 0.007) and TNF-α (OR = 1.81, 95% CI = 1.26 to 2.61, P = 0.001). CONCLUSIONS: Our data suggest that treatment with an antibiotic cocktail lasting 1 week is sufficient to induce a significant reduction in gut microbes. 3 weeks of antibiotic exposure can lead to the colonization of persistant microbiota and cause changes in intestinal tissue and local immune responses.

Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE.

BACKGROUND: Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented. METHODS: Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6-12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles. RESULTS: 367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding. CONCLUSIONS: Rivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions. TRIAL REGISTRATION: NCT00439725 and NCT02064439.

Unsupervised machine learning cluster analysis to identification EVAR patients clinical phenotypes based on radiomics.

OBJECTIVE: This study used unsupervised machine learning (UML) cluster analysis to explore clinical phenotypes of endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) patients based on radiomics. METHOD: We retrospectively reviewed 1785 patients with infra-renal AAA who underwent elective EVAR procedures between January 2010 and December 2020. Pyradiomics was used to extract the radiomics features. Statistical analysis was applied to determine the radiomics features that related to severe adverse events (SAEs) after EVAR. The selected features were used for UML cluster analysis in training set and validation in test set. Comparison of basic characteristics and radiomics features of different clusters. The Kaplan-Meier analysis was conducted to generate the cumulative incidence of freedom from SAEs rate. RESULT: A total of 1180 patients were enrolled. During the follow-up, 353 patients experienced EVAR-related SAEs. In total, 1223 radiomics features were extracted from each patient, of which 23 radiomics features were finally preserved to identify different clinical phenotypes. 944 patients were allocated to the training set. Three clusters were identified in training set, in which patients had identical clinical characteristics and morphological features, while varied considerably of selected radiomics features. This encouraging performance was further approved in the test set. In addition, each cluster was well differentiated from other clusters and Kaplan-Meier analysis showed significant differences of freedom from SAEs rate between different clusters both in the training (p = .0216) and test sets (p = .0253). CONCLUSION: Based on radiomics, UML cluster analysis can identify clinical phenotypes in EVAR patients with distinct long-term outcomes.

A taurine-based hydrogel with the neuroprotective effect and the ability to promote neural stem cell proliferation.

Ischemic stroke, a cerebrovascular disease caused by arterial occlusion in the brain, can lead to brain impairment and even death. Stem cell therapies have shown positive advantages to treat ischemic stroke because of their extended time window, but the cell viability is poor when transplanted into the brain directly. Therefore, a new hydrogel GelMA-T was developed by introducing taurine on GelMA to transplant neural stem cells. The GelMA-T displayed the desired photocuring ability, micropore structure, and cytocompatibility. Its compressive modulus was more similar to neural tissue compared to that of GelMA. The GelMA-T could protect SH-SY5Y cells from injury induced by OGD/R. Furthermore, the NE-4C cells showed better proliferation performance in GelMA-T than that in GelMA during both 2D and 3D cultures. All results demonstrate that GelMA-T possesses a neuroprotective effect for ischemia/reperfusion injury against ischemic stroke and plays a positive role in promoting NSC proliferation. The novel hydrogel is anticipated to function as cell vehicles for the transplantation of neural stem cells into the stroke cavity, aiming to treat ischemic stroke.

Fabrication of lignosulfonate-derived porous carbon via pH-tunable self-assembly strategy for efficient atrazine removal.

Herein, a straightforward protocol was developed for the one-pot synthesis of N-doped lignosulfonate-derived carbons (NLDCs) with a tunable porous structure using natural amino acids-templated self-assembly strategy. Specifically, histidine was employed as a template reagent, leading to the preparation of 10-NLDC-21 with remarkable characteristics, including the large specific surface area (SBET = 1844.5 m2/g), pore volume (Vmes = 1.22 cm3/g) and efficient adsorption for atrazine (ATZ) removal. The adsorption behavior of ATZ by NLDCs followed the Langmuir and pseudo-second-order models, suggesting a monolayer chemisorption nature of ATZ adsorption with the maximum adsorption capacity reached up to 265.77 mg/g. Furthermore, NLDCs exhibited excellent environmental adaptability and recycling performance. The robust affinity could be attributed to multi-interactions including pore filling, electrostatic attraction, hydrogen bonding and π-π stacking between the adsorbents and ATZ molecules. This approach offers a practical method for exploring innovative bio-carbon materials for sewage treatment.

Synthesis of Pyrimido[1,2-a]indolediones and Pyrimidinediones via [4+2] Annulation of 2H-Azirine-2-carbaldehydes.

NHC-catalyzed [4+2] annulation of 2H-azirine-2-carbaldehydes with ketimines and isocyanates has been developed, providing straightforward synthetic protocols for constructing structurally intriguing pyrimido[1,2-a]indolediones and pyrimidinediones under mild conditions with excellent yields. This protocol can be used to synthesize the core skeleton of pharmaceutically important drugs and pyrimido[1,2-a]indoledione-containing natural products, making it potentially valuable for creating biologically active derivatives.

1T'-transition metal dichalcogenide monolayers stabilized on 4H-Au nanowires for ultrasensitive SERS detection.

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

A Modulation Method for Tunnel Magnetoresistance Current Sensors Noise Suppression.

To mitigate the impact of low-frequency noise from the tunnel magnetoresistance (TMR) current sensor and ambient stray magnetic fields on weak current detection accuracy, we propose a high-resolution modulation-demodulation test method. This method modulates and demodulates the measurement signal, shifting low-frequency noise to the high-frequency band for effective filtering, thereby isolating the target signal from the noise. In this study, we developed a Simulink model for the TMR current sensor modulation-demodulation test method. Practical time-domain and frequency-domain tests of the developed high-resolution modulation-demodulation method revealed that the TMR current sensor exhibits a nonlinearity as low as 0.045%, an enhanced signal-to-noise ratio (SNR) of 77 dB, and a heightened resolution of 100 nA. The findings indicate that this modulation-demodulation test method effectively reduces the impact of low-frequency noise on TMR current sensors and can be extended to other types of resistive devices.

Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

Phase Engineering of Nanomaterials: Transition Metal Dichalcogenides.

Crystal phase, a critical structural characteristic beyond the morphology, size, dimension, facet, etc., determines the physicochemical properties of nanomaterials. As a group of layered nanomaterials with polymorphs, transition metal dichalcogenides (TMDs) have attracted intensive research attention due to their phase-dependent properties. Therefore, great efforts have been devoted to the phase engineering of TMDs to synthesize TMDs with controlled phases, especially unconventional/metastable phases, for various applications in electronics, optoelectronics, catalysis, biomedicine, energy storage and conversion, and ferroelectrics. Considering the significant progress in the synthesis and applications of TMDs, we believe that a comprehensive review on the phase engineering of TMDs is critical to promote their fundamental studies and practical applications. This Review aims to provide a comprehensive introduction and discussion on the crystal structures, synthetic strategies, and phase-dependent properties and applications of TMDs. Finally, our perspectives on the challenges and opportunities in phase engineering of TMDs will also be discussed.

The real-world incidence and predictors of sac regression in patients with infrarenal abdominal aortic aneurysm after standard EVAR.

OBJECTIVE: Sac regression (SR) is a surrogate marker of satisfied endovascular aneurysm repair (EVAR). This research aims to investigate the incidence and predictors of SR in a Chinese population. DESIGN: Single centre retrospective cohort study. METHODS: Consecutive patients with infrarenal abdominal aortic aneurysms (AAAs) who underwent standard EVAR were retrospectively reviewed. SR was defined as sac shrinkage > 5 mm on computed tomography images, while major SR (MaSR) was ≥ 10 mm sac shrinkage. The cumulative rate was calculated by Kaplan-Meier analysis and predictors were identified by the Cox regression model. RESULTS: A total of 469 patients (median age, 71 years old) were included. The majority of them (86.6 %) were male. With a median time of 13.6 months, SR was detected in 129 (27.5 %) patients after the index EVAR. Compared with never smokers, current smokers were more likely to experience SR (adjusted HR 2.630, p < .001), while former smokers did not show any significant difference. Multivariate Cox regression also showed that maximal aneurysm diameter (adjusted HR 1.012, p = 0.035) and female (adjusted HR 1.675, p = .045) were independent predictors of SR. A total of 51 (10.9 %) patients had MaSR at a median time of 15.4 months after EVAR. In multivariate analysis, maximal aneurysm diameter and Zenith stent graft were independently associated with MaSR. CONCLUSION: In Chinese population, the incidence of SR and MaSR was 27.5 % and 10.9 % after EVAR, respectively. Maximal aneurysm diameter and female were independent predictors of SR. Compared with never smokers, it was more likely to have SR in current smokers.

Synthesis of Pyridazino[4,5-b]indoles by [3+3] Annulation of 2-Alkenylindoles and Hydrazonyl Chlorides.

A novel [3+3] annulation reaction of 2-alkenylindoles with hydrazonyl chlorides in the presence of base for the formation of pyridazino[4,5-b]indoles was developed. This approach provided a convenient and efficient way to synthesize a series of functionalized pyridazino[4,5-b]indoles derivatives. The method exhibited a broad substrate scope and provided the corresponding pyridazino[4,5-b]indoles products with excellent yields.

HBV integrations reshaping genomic structures promote hepatocellular carcinoma.

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.

The Impact of Balloon Pre-dilatation Techniques on Drug-Coated Balloon Therapy for Femoropopliteal Artery Disease: Six-Month Results From the CIVILIAN Registry.

OBJECTIVE: The purpose of this study is to compare the initial outcomes of using the Chocolate balloon pre-dilatation (CLP) and sequential enlarging angioplasty pre-dilatation (sequential balloon pre-dilation [SP]) techniques versus the conventional balloon pre-dilatation (CP) method prior to drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions. METHODS: This was a retrospective analysis of prospectively collected data from the CIVILIAN (Clinical InVestigation of different lesIon preparation modaLIty followed by DCB in femoropopliteal Artery occlusioN disease) registry. Between March 2021 and November 2022, 3 pre-dilation techniques used prior to the DCB angioplasty were included. The study endpoint included intraoperative finial severe dissection after provisional stent placement, bailout stenting rate, the diameter of the largest pre-dilation balloon and DCB, as well as major adverse events (MAEs), including death, major limb amputation, or target vessel revascularization at 6 months. RESULTS: During the study period, 435 limbs (429 patients) were pre-dilated before DCB treatment in FP lesions, 166 limbs were pre-dilated with Chocolate balloons, 93 limbs with sequential enlarging balloon pre-dilation technique, and 176 limbs with CP. The largest pre-dilation balloon was significantly larger in CLP and SP groups than that in the CP group (CLP 4.74±0.52 mm vs CP 4.36±0.64 mm, p<0.001; SP 4.82±0.69 mm vs CP 4.36±0.63 mm, p<0.001). A consistent result was shown in DCB diameter (CLP 4.86±0.44 mm vs CP 4.71±0.51 mm, p=0.003; SP 4.90±0.58 mm vs CP 4.71±0.51 mm, p=0.006). The bailout stenting rate was significantly lower in the CLP group than that in the CP group (18.1% vs 30.1%, p=0.011). The rates of MAEs at 6 months in the CLP and SP groups were comparable to those in the CP group (7.2% and 8.6% vs 6.3%, p>0.05). The risk for intraoperative bailout stenting rate was related to TASC D classification (3.59, 95% CI: 1.83-7.05, p<0.001), chronic total occlusion (CTO) lesion (1.82, 95% CI: 1.07-3.10, p=0.028), as well as pre-dilated with the conventional balloon (1.64, 95% CI: 1.00-2.69, p=0.048). CONCLUSIONS: By utilizing chocolate balloon and sequential enlarging angioplasty, it becomes possible to use larger pre-dilation balloons and DCBs. In addition, the use of the chocolate balloon can significantly reduce the need for bailout stenting when compared with conventional balloons. CLINICAL IMPACT: The utilization of a chocolate balloon and sequential enlarging angioplasty has emerged as a promising technique for angioplasty procedures. This approach allows for the use of larger pre-dilation balloons and drug-coated balloons. The use of the chocolate balloon can significantly reduce the need for bail-out stenting when compared to conventional balloons. Further research is required to determine the impact of vessel preparation techniques on the primary patency.

Principles of Optimal Antithrombotic Therapy for Iliac VEnous Stenting (POATIVES): A national expert-based Delphi consensus study.

OBJECTIVE: Management of antithrombotic therapy in patients undergoing venous stents has not yet reached consensus, and there are not any recommendations from published guidelines. We undertook a Delphi consensus from Chinese experts to develop recommendations regarding the preferred antithrombotic therapy in patients following venous stenting. METHODS: The phase 1 questionnaire was comprised of three clinical scenarios of venous stenting for non-thrombotic iliac vein lesions (NIVL), acute deep vein thrombosis (DVT), and post-thrombotic syndrome (PTS) and was sent to venous practitioners across China. In phase 2, the results of phase 1 were distributed to a panel of experts for evaluation along with a questionnaire encompassing a series of statements produced during phase 1. A modified Delphi method was used to reach consensus on recommendations through two rounds of surveys. RESULTS: The phase 1 questionnaire was completed by 283 respondents. In phase 2, an expert panel consisting of 28 vascular surgeons and interventional radiologists was assembled and voted 17 statements relating to antithrombotic management after venous stenting for NIVL (4 statements), DVT (6 statements), and PTS (7 statements). The majority of the statements about the antithrombotic agent selection received a high consensus strength. CONCLUSIONS: Based on the national Delphi consensus of Chinese experts regarding antithrombotic therapy following iliac venous stenting in three common scenarios, most of the statements could be used to guide antithrombotic management following venous stenting. Further studies are required to clarify controversial issues including the dose and duration of anticoagulants, the role of antiplatelet agents, especially in patients with NIVL.