Retinal honeycomb appearance and its role in patients with X-linked retinoschisis.

BACKGROUND: To investigate the clinical characteristics of retinal honeycomb appearance in a large cohort of patients with X-linked retinoschisis (XLRS) and to determine whether it is associated with complications like retinal detachment (RD) and vitreous hemorrhage (VH). METHODS: A retrospective observational case series. A chart review of medical records, wide-field fundus imaging, and optical coherence tomography (OCT) was performed on 78 patients (153 eyes) diagnosed with XLRS at Beijing Tongren eye center between Dec 2017 and Feb 2022. The chi-square test or Fisher exact test was performed on the 2 × 2 cross-tabulations of honeycomb appearance and other peripheral retinal findings and complications. RESULTS: Thirty-eight patients (48.7%), and 60 eyes (39.2%) had a honeycomb appearance of different areas on the fundus. The supratemporal quadrant was the most commonly affected (45 eyes, 75.0%), followed by the infratemporal (23 eyes, 38.3%), the infranasal (10 eyes,16.7%), and supranasal (9 eyes,15.0%). The appearance was significantly associated with peripheral retinoschisis, inner retinal layer break, outer retinal layer break, RD, and rhegmatogenous retinal detachment (RRD) (p < 0.01, p = 0.032, p < 0.01, p = 0.008, p < 0.01, respectively). All the eyes complicated with RRD had the appearance. None of the eyes without the appearance had RRD. CONCLUSIONS: The data suggest that the honeycomb appearance is not uncommon in patients with XLRS and is more likely to be accompanied by an RRD, and inner and outer layer breaks, thus should be treated with caution and close observation.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Identification of High-Risk Coronary Lesions by 3-Vessel Optical Coherence Tomography.

BACKGROUND: Optical coherence tomography (OCT) may provide a method for detecting histologically defined high-risk plaques in vivo. OBJECTIVES: The authors aimed to investigate the prognostic value of OCT for identifying patients and lesions that are at risk for adverse cardiac events. METHODS: Between January 2017 and May 2019, OCT of all the 3 main epicardial arteries was performed in 883 patients with acute myocardial infarction (MI) who were referred for primary percutaneous coronary intervention. The primary endpoint was the composite of cardiac death, nonculprit lesion-related nonfatal MI, and unplanned coronary revascularization. Patients were followed for up to 4 years (median 3.3 years). RESULTS: The 4-year cumulative rate of the primary endpoint was 7.2%. In patient-level analysis, thin-cap fibroatheroma (TCFA) (adjusted HR: 3.05; 95% CI: 1.67-5.57) and minimal lumen area (MLA) <3.5 mm2 (adjusted HR: 3.71; 95% CI: 1.22-11.34) were independent predictors of the primary endpoint. In lesion-level analysis, nonculprit lesions responsible for subsequent events were not angiographically severe at baseline (mean diameter stenosis 43.8% ± 13.4%). TCFA (adjusted HR: 8.15; 95% CI: 3.67-18.07) and MLA <3.5 mm2 (adjusted HR: 4.33; 95% CI: 1.81-10.38) were predictive of events arising from each specific lesion. TCFAs with an MLA <3.5 mm2 carried a higher risk and were sufficient for identifying patients at risk for the composite of cardiac death and nonculprit lesion-related nonfatal MI. CONCLUSIONS: OCT imaging of angiographically nonobstructive territories in patients with acute MI can aid in identifying patients and lesions at increased risk for adverse cardiac events.

Creatinase: Using Increased Entropy to Improve the Activity and Thermostability.

Improving protein thermostability in mutagenesis-based enzyme engineering was often achieved by enhancing interresidue interactions via mutation to increase the enthalpy penalty of unfolding. However, this approach may trade off the functional activity due to the loss of structural flexibility of the biomolecule. Here, by performing X-ray crystallography, enzymatic kinetic experiments, neutron scattering, and thermodynamical measurements, we compared the structures, catalytic behaviors, dynamics, and thermostability between a wild-type creatinase and its four-point mutant. We found that the mutant is an entropy-driven thermostable protein with higher structural flexibility, i.e., higher conformational entropy, in the folded state compared to the wild type. The increased conformational entropy of the mutant in the folded state can reduce the entropy gain during unfolding and thus renders it greater thermostability. Moreover, the increased structural flexibility, particularly around the catalytic site, can broaden the mutant's working temperature range and considerably improve its activity at ambient conditions, which is crucial for its application in diagnosing kidney diseases. Complementary all-atom molecular dynamics simulations indicated that the four mutations replaced several of the strong interresidue interactions (electrostatic interactions and hydrogen bonds) with weak hydrophobic interactions. These substitutions not only release the structural flexibility to promote the thermostability and enzymatic activity of the protein but they also preserve the protein structure from collapsing. Our findings may pave a route for the entropy-driven strategy to design proteins with high thermostability and activity.

Potent bromodomain and extraterminal domain inhibitor JAB-8263 suppresses MYC expression and exerts anti-tumor activity in colorectal cancer models.

BACKGROUND: The overexpression of the MYC gene plays an important role in the occurrence, development and evolution of colorectal cancer (CRC). Bromodomain and extraterminal domain (BET) inhibitors can decrease the function BET by recognizing acetylated lysine residues, thereby downregulating the expression of MYC. AIM: To investigate the inhibitory effect and mechanism of a BET inhibitor on CRC cells. METHODS: The effect of the BET inhibitor JAB-8263 on the proliferation of various CRC cell lines was studied by CellTiter-Glo method and colony formation assay. The effect of JAB-8263 on the cell cycle and apoptosis of CRC cells was studied by propidium iodide staining and Annexin V/propidium iodide flow assay, respectively. The effect of JAB-8263 on the expression of c-MYC, p21 and p16 in CRC cells was detected by western blotting assay. The anti-tumor effect of JAB-8263 on CRC cells in vivo and evaluation of the safety of the compound was predicted by constructing a CRC cell animal tumor model. RESULTS: JAB-8263 dose-dependently suppressed CRC cell proliferation and colony formation in vitro. The MYC signaling pathway was dose-dependently inhibited by JAB-8263 in human CRC cell lines. JAB-8263 dose-dependently induced cell cycle arrest and apoptosis in the MC38 cell line. SW837 xenograft model was treated with JAB-8263 (0.3 mg/kg for 29 d), and the average tumor volume was significantly decreased compared to the vehicle control group (P < 0.001). The MC38 syngeneic murine model was treated with JAB-8263 (0.2 mg/kg for 29 d), and the average tumor volume was significantly decreased compared to the vehicle control group (P = 0.003). CONCLUSION: BET could be a potential effective drug target for suppressing CRC growth, and the BET inhibitor JAB-8263 can effectively suppress c-MYC expression and exert anti-tumor activity in CRC models.

The effects of short-term dietary exposure to SiO2 nanoparticle on the domesticated lepidopteran insect model silkworm (Bombyx mori): Evidence from the perspective of multi-omics.

Silicon dioxide nanoparticles (nSiO2) are one of the widely utilized nanoparticle (NPSs) materials, and exposure to nSiO2 is ubiquitous. With the increasing commercialization of nSiO2, the potential risk of nSiO2 release to the health and the ecological environment have been attracted more attention. In this study, the domesticated lepidopteran insect model silkworm (Bombyx mori) was utilized to evaluate the biological effects of dietary exposure to nSiO2. Histological investigations showed that nSiO2 exposure resulted in midgut tissue injury in a dose-dependent manner. Larval body mass and cocoon production were reduced by nSiO2 exposure. ROS burst was not triggered, and the activities of antioxidant enzymes were induced in the midgut of silkworm exposure to nSiO2. RNA-sequencing revealed that the differentially expressed genes induced by nSiO2 exposure were predominantly enriched into xenobiotics biodegradation and metabolism, lipid, and amino acid metabolism pathways. 16 S rDNA sequencing revealed that nSiO2 exposure altered the microbial diversity in the gut of the silkworm. Metabolomics analysis showed that the combined uni- and multivariate analysis identified 28 significant differential metabolites from the OPLS-DA model. These significant differential metabolites were predominantly enriched into the metabolic pathways, including purine metabolism and tyrosine metabolism and so. Spearman correlation analysis and the Sankey diagram established the relationship between microbe and metabolites, and some genera may play crucial and pleiotropic functions in the interaction between microbiome and host. These findings indicated that nSiO2 exposure could impact the dysregulation of genes related to xenobiotics metabolism, gut dysbiosis, and metabolic pathways and provided a valuable reference for assessing nSiO2 toxicity from a multi-dimensional perspective.

TRAIL or TRAIL-R2 as a predictive biomarker for mortality or cardiovascular events: A systematic review and meta-analysis.

ABSTRACT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TRAIL-receptor-2 (TRAIL-R2) are associated with atherosclerosis. This meta-analysis aimed to investigate the potential association between TRAIL/TRAIL-R2 with mortality or cardiovascular (CV) events. PubMed, Embase, and the Cochrane Library were searched for reports published up to May 2021. Reports were included when the association between TRAIL or TRAIL-R2 and mortality or cardiovascular events was reported. Considering the heterogeneity between studies, we used the random-effects model for all analyses. Ultimately, the meta-analysis included 18 studies (16,295 patients). The average follow-up ranged from 0.25 to 10 years. Decreased TRAIL levels were negatively associated with all-cause mortality (rank variable, HR, 95% CI: 2.93, 1.94-4.42; I 2 =0.0%, P heterogeneity =0.835). Increased TRAIL-R2 levels were positively associated with all-cause mortality (continuous variable, HR, 95% CI: 1.43, 1.23-1.65; I 2 =0.0%, P heterogeneity =0.548; rank variable, HR, 95% CI: 7.08, 2.70-18.56; I 2 =46.5%, P heterogeneity =0.154), CV mortality (continuous variable, HR, 95% CI: 1.33, 1.14-1.57; I 2 =0.0%, P heterogeneity =0.435), myocardial infarction (continuous variable, HR, 95% CI: 1.23, 1.02-1.49; rank variable, HR, 95% CI: 1.49, 1.26-1.76; I 2 =0.7%, P heterogeneity =0.402), and new-onset heart failure (rank variable, HR, 95% CI: 3.23, 1.32-7.87; I 2 =83.0%, P heterogeneity =0.003).In conclusion, decreased TRAIL was negatively associated with all-cause mortality and increasedTRAIL-R2 was positively associated with all-cause mortality, CV mortality, myocardial infarction, and heart failure.

Icariin alleviates autistic-like behavior, hippocampal inflammation and vGlut1 expression in adult BTBR mice.

Autism spectrum disorder (ASD) is a complicated, heterogeneous disorder characterized by social interaction deficits and repetitive stereotypical behaviors. Neuroinflammation and synaptic protein dysregulation have been implicated in ASD pathogenesis. Icariin (ICA) has proven to exert neuroprotective function through anti-inflammatory function. Therefore, this study aimed to clarify the effects of ICA treatment on autism-like behavioral deficits in BTBR mice and whether these changes were related to modifications in the hippocampal inflammation and the balance of excitatory/inhibitory synapses. ICA supplementation (80 mg/kg, once daily for ten days, i.g.) ameliorated social deficits, repetitive stereotypical behaviors, and short-term memory deficit without affecting locomotor activity or anxiety-like behaviors of BTBR mice. Furthermore, ICA treatment inhibited neuroinflammation via decreasing microglia number and the soma size in the CA1 region of the hippocampus, as well as the protein levels of proinflammatory cytokines in the hippocampus of BTBR mice. In addition, ICA treatment also rescued excitatory-inhibitory synaptic protein imbalance by inhibiting the increased vGlut1 level without affecting the vGAT level in the BTBR mouse hippocampus. Collectively, the observed results indicate that ICA treatment alleviates ASD-like features, mitigates disturbed balance of excitatory-inhibitory synaptic protein, and inhibits hippocampal inflammation in BTBR mice, and may represent a novel promising drug for ASD treatment.

SERS-based immunomagnetic bead for rapid detection of H5N1 influenza virus.

The surface-enhanced Raman scattering (SERS) has recently drawn attention in the detection of respiratory viruses, but there have been few reports of the direct detection of viruses. In this study, a sandwich immunomagnetic bead SERS was established for the rapid diagnosis of the H5N1 influenza virus. The detection limit was estimated to be 5.0 × 10-6 TCID50/ml. The method showed excellent specificity with no cross-reaction with H1N1, H5N6 or H9N2. The H5N1 influenza virus detection accuracy of the SERS method was 100% in chicken embryos. The results hold great promise for the utilization of SERS as an innovative approach in the diagnosis of influenza virus.

Proxalutamide in metastatic castration-resistant prostate cancer: primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100 mg, 200 mg, 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%), and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n=37), 200 mg (n=33), and 300 mg (n=35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were respectively achieved in 100 mg, 200 mg, 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥ grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial. This article is protected by copyright. All rights reserved.

First-in-Man Use of a Modified Controller to Resolve HVAD Failure-to-Restart.

We report a case of Medtronic HeartWare ventricular assist device (HVAD) pump failure-to-restart. Despite HVAD withdrawal from the market in June 2021, up to 4,000 patients remain on HVAD support worldwide, and many are at high risk for this serious complication. This report describes the first-in-man use of a new HVAD controller that restarted a defective HVAD pump and avoided a fatal outcome. This new controller has the potential of preventing unnecessary VAD exchanges and saving lives.

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns.

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (-16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3-5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.

Neoadjuvant Therapy with Immune Checkpoint Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown great promise in treating late-stage gastric cancer, but their efficacy in the neoadjuvant setting has not been studied in large cohorts. Here, we explored the efficacy and safety of neoadjuvant ICI-based therapy in locally advanced gastric cancer. PATIENTS AND METHODS: We included studies containing patients with locally advanced gastric/gastroesophageal cancer who received ICI-based neoadjuvant therapy. We searched PubMed, Embase, Cochrane library, and abstracts from major international oncology conferences. We performed this meta-analysis using the META package in R.3.6.1. RESULTS: Twenty-one prospective phase I/II studies comprising 687 patients were identified. The pathological complete response (pCR) rate was 0.21 (95% CI 0.18-0.24), major pathological response (MPR) rate was 0.41 (95% CI 0.31-0.52), and R0 resection rate was 0.94 (95% CI 0.92-0.96). The efficacy was highest with ICI plus radiochemotherapy, lowest with ICI alone, and in the middle with ICI and chemotherapy ± anti-angiogenesis. dMMR/MSI-H and PD-L1-high patients benefited more than pMMR/MSS and PD-L1-low patients. Grade 3 or higher toxicity rate was 0.23 (95% CI 0.13-0.38). These results exceeded those in trials of neoadjuvant chemotherapy, where the rate of pCR was 0.08 (95% CI 0.06-0.11), MPR was 0.22 (95% CI 0.19-0.26), R0 section was 0.84 (95% CI 0.80-0.87), and overall grade 3 or higher toxicity was 0.28 (95% CI 0.13-0.47) in 4800 patients across 21 studies. CONCLUSIONS: In summary, the integrated results show promising efficacy and safety of ICI-based neoadjuvant therapy for locally advanced gastric cancer and support further investigation in large multicenter randomized trials.

Enzyme-Assisted Nucleic Acid Amplification in Molecular Diagnosis: A Review.

Infectious diseases and tumors have become the biggest medical challenges in the 21st century. They are driven by multiple factors such as population growth, aging, climate change, genetic predispositions and more. Nucleic acid amplification technologies (NAATs) are used for rapid and accurate diagnostic testing, providing critical information in order to facilitate better follow-up treatment and prognosis. NAATs are widely used due their high sensitivity, specificity, rapid amplification and detection. It should be noted that different NAATs can be selected according to different environments and research fields; for example, isothermal amplification with a simple operation can be preferred in developing countries or resource-poor areas. In the field of translational medicine, CRISPR has shown great prospects. The core component of NAAT lies in the activity of different enzymes. As the most critical material of nucleic acid amplification, the key role of the enzyme is self-evident, playing the upmost important role in molecular diagnosis. In this review, several common enzymes used in NAATs are compared and described in detail. Furthermore, we summarize both the advances and common issues of NAATs in clinical application.

Advances in materials-based therapeutic strategies against osteoporosis.

Osteoporosis is caused by the disruption in homeostasis between bone formation and bone resorption. Conventional management of osteoporosis involves systematic drug administration and hormonal therapy. These treatment strategies have limited curative efficacy and multiple adverse effects. Biomaterials-based therapeutic strategies have recently emerged as promising alternatives for the treatment of osteoporosis. The present review summarizes the current status of biomaterials designed for managing osteoporosis. The advantages of biomaterials-based strategies over conventional systematic drug treatment are presented. Different anti-osteoporotic delivery systems are concisely addressed. These materials include injectable hydrogels and nanoparticles, as well as anti-osteoporotic bone tissue engineering materials. Fabrication techniques such as 3D printing, electrostatic spinning and artificial intelligence are appraised in the context of how the use of these adjunctive techniques may improve treatment efficacy. The limitations of existing biomaterials are critically analyzed, together with deliberation of the future directions in biomaterials-based therapies. The latter include discussion on the use of combination strategies to enhance therapeutic efficacy in the osteoporosis niche.

Screening of phosphorus solubilizing microorganisms in cold environment and their effects on the growth of Brassica napus.

To screen out phosphorus solubilizing strains that can adapt to cold climate in Qinghai Province, Bacillus mucilaginosus, B. megaterium, B. cereus, Streptomyces violovariabilis, S. cinnamofuscus, and S. flavoagglomeratus were screened with solid plate medium as the primary and liquid medium as the secondary screening, with calcium phosphate, lecithin, and phytic acid as the single source of phosphorus. By comprehensively comparing the size of phosphate solubilizing circle in the solid plate medium and the soluble phosphorus content in the liquid medium, three strains of phosphate solubilizing bacteria with good phosphate solubilizing effects were screened, S. violovariabilis, S. cinnamofuscus, and B. mucilaginosus. The three phosphate solubilizing bacteria were made into liquid ino-culants, and the small rapeseed pot experiment was carried out with two soils with different fertilities in a cold climate in September. Compared with the control, plant height, fresh weight, root length, and root weight of rapes in high-fertility cultivated soil increased by 35.5%, 191.0%, 26.2%, and 282.7%, while plant phosphorus absorption, total phosphorus and available phosphorus contents in the rhizosphere soil increased by 968.9%, 5.1%, and 2.1%, respectively. In low-fertility soil, plant height and fresh weight was increased by 45.8% and 61.3%, root length and weight was decreased by 2.6% and 4.4%, while plant phosphorus absorption and the contents of total P and available P in rhizosphere soil were increased by 91.5 %, 29.1%, and 213.7%, respectively. The effect of the other two inoculants treatments was less significant than S. violovariabilis. Therefore, S. violovariabilis was the phosphate solubilizing strain suitable for the cold climate in Qinghai.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n=498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and three linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary endpoint is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Target tumor therapy in human gastric cancer cells through the combination of docetaxel-loaded cationic lipid microbubbles and ultrasound-triggered microbubble destruction.

It is well accepted that ultrasound-induced microbubble (USMB) cavitation is a promising method for drug delivery. Ultrasound-targeted destruction of cytotoxic drug-loaded lipid microbubbles (LMs) is used to promote the treatment of cancer. This study aimed to investigate the antitumor effects from a combination of docetaxel-loaded cationic lipid microbubbles (DLLM+) and ultrasound (US)-triggered microbubble destruction (UTMD) on gastric cancer (GC). It was found that the functional dose of DOC in this study was 1 × 10-9 mol/L. We found that DLLM combined with the UTMD group showed greater growth inhibition of the cultured human gastric cancer cells (HGCCs) when compared with the other five groups by arresting the G2/M phase in the cell cycle. However, DLLM+ combined with UTMD showed a higher inhibition rate of tumor growth than DLLM combined with UTMD and that of the RC/CMV-p16 combined with UTMD in vitro and in vivo experiments. DLLM+ combined with UTMD significantly suppressed proliferation and promoted the apoptosis of HGCCs with more cells arrested in the G2/M phase. In addition, DLLM+ combined with UTMD suppressed the proliferation and induced apoptosis by arresting cells in the G2/M phase, which led to a great inhibition of GC progression. Thus, our results indicated that the combination of DLLM+ and UTMD might represent a novel and promising approach to chemotherapy for GC.

Predicting prognosis of nasopharyngeal carcinoma based on deep learning: peritumoral region should be valued.

BACKGROUND: The purpose of this study was to explore whether incorporating the peritumoral region to train deep neural networks could improve the performance of the models for predicting the prognosis of NPC. METHODS: A total of 381 NPC patients who were divided into high- and low-risk groups according to progression-free survival were retrospectively included. Deeplab v3 and U-Net were trained to build segmentation models for the automatic segmentation of the tumor and suspicious lymph nodes. Five datasets were constructed by expanding 5, 10, 20, 40, and 60 pixels outward from the edge of the automatically segmented region. Inception-Resnet-V2, ECA-ResNet50t, EfficientNet-B3, and EfficientNet-B0 were trained with the original, segmented, and the five new constructed datasets to establish the classification models. The receiver operating characteristic curve was used to evaluate the performance of each model. RESULTS: The Dice coefficients of Deeplab v3 and U-Net were 0.741(95%CI:0.722-0.760) and 0.737(95%CI:0.720-0.754), respectively. The average areas under the curve (aAUCs) of deep learning models for classification trained with the original and segmented images and with images expanded by 5, 10, 20, 40, and 60 pixels were 0.717 ± 0.043, 0.739 ± 0.016, 0.760 ± 0.010, 0.768 ± 0.018, 0.802 ± 0.013, 0.782 ± 0.039, and 0.753 ± 0.014, respectively. The models trained with the images expanded by 20 pixels obtained the best performance. CONCLUSIONS: The peritumoral region NPC contains information related to prognosis, and the incorporation of this region could improve the performance of deep learning models for prognosis prediction.