Eu(III) functionalized ZnMOF based efficient dual-emission sensor integrated with self-calibrating logic gate for intelligent detection of epinephrine.

The rapid detection of epinephrine (EPI) in serum holds immense importance in the early disease diagnosis and regular monitoring. On the basis of the coordination post-synthetic modification (PSM) strategy, a Eu3+ functionalized ZnMOF (Eu3+@ZnMOF) was fabricated by anchoring the Eu3+ ions within the microchannels of ZnMOF as secondary luminescent centers. Benefiting from two independent luminescent centers, the prepared Eu3+@ZnMOF shows great potential as a multi-signal self-calibrating luminescent sensor in visually and efficiently detecting serum EPI levels, with high reliability, fast response time, excellentrecycleability, and low detection limits of 17.8 ng/mL. Additionally, an intelligent sensing system was designed in accurately and reliably detecting serum EPI levels, based on the designed self-calibrating logic gates. Furthermore, the possible sensing mechanisms were elucidated through theoretical calculations as well as spectral overlaps. This work provides an effective and promising strategy for developing MOFs-based self-calibrating intelligent sensing platforms to detect bioactive molecules in bodily fluids.

Potential Underestimation of Left Ventricular Mechanical Dyssynchrony in Dyssynchrony and Outcomes Assessment.

Objective: Left ventricular (LV) mechanical dyssynchrony (LVMD) is fundamental to the progression of heart failure and ventricular remodeling. The status of LVMD in different patterns of bundle branch blocks (BBB) is unclear. In this study, we analyzed the relationship between LVMD and left ventricular systolic dysfunction using real-time three-dimensional echocardiography (RT-3DE). Methods: RT-3DE and conventional two-dimensional echocardiography were performed on 68 patients with left bundle branch block (LBBB group), 106 patients with right bundle branch block (RBBB group), and 103 patients without BBB (Normal group). The RT-3DE data sets provided time-volume analysis for global and segmental LV volumes. The LV systolic dyssynchrony index (LVSDI) was calculated using the standard deviation (SD) and maximal difference (Dif) of time to minimum segmental volume (tmsv) for LV segments adjusted by the R-R interval. LVMD was considered if the LVSDI (Tmsv-16-SD) was greater than or equal to 5%. Results: LVSDI is negatively and significantly correlated with left ventricular ejection fraction (LVEF), but not with BBB or QRS duration. The proportion of LVMD in the LBBB, RBBB, and Normal group was 30.88%, 28.30%, and 25.24%, respectively, and there was no significant difference. Conclusion: In dilated cardiomyopathy, LVMD is more closely related to LVEF reduction than QRS morphology and duration.

Extraction, purification, structural features, modifications, bioactivities, structure-activity relationships, and applications of polysaccharides from garlic: A review.

Garlic is a common vegetable and spice in people's daily diets, in which garlic polysaccharide (GP) is one of the most important active components with a variety of benefits, such as antioxidant, immune-enhancing, anti-inflammatory, liver-protective and bowel-regulating properties. >20 types of GPs, mainly crude polysaccharides, have been identified. However, the exact chemical composition of GPs or the mechanism underlying their pharmacological activity is still not fully understood. The extraction and purification methods of GPs are compared in this review while providing detailed information on their structural features, identification methods, major biological activities, mechanisms of actions, structural modifications, structure-activity relationships as well as potential applications. Finally, the limitations of GP research and future issues that need to be addressed are discussed in this review. GPs are widely recognized as substances with great potential in the pharmaceutical and food industries. Therefore, this review aims to provide a comprehensive summary of the latest research progresses in the field of GPs, together with scientific insights and a theoretical support for the development of GPs in research and industrialization.

RGA1 regulates grain size, rice quality and seed germination in the small and round grain mutant srg5.

BACKGROUND: Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. RESULTS: In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. CONCLUSIONS: These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Novel Scaffold Agonists of the α2A Adrenergic Receptor Identified via Ensemble-Based Strategy.

The α2A adrenergic receptor (α2A-AR) serves as a critical molecular target for sedatives and analgesics. However, α2A-AR ligands with an imidazole ring also interact with an imidazoline receptor as well as other proteins and lead to undesirable effects, motivating us to develop more novel scaffold α2A-AR ligands. For this purpose, we employed an ensemble-based ligand discovery strategy, integrating long-term molecular dynamics (MD) simulations and virtual screening, to identify new potential α2A-AR agonists with novel scaffold. Our results showed that compounds SY-15 and SY-17 exhibited significant biological effects in the preliminary evaluation of protein kinase A (PKA) redistribution assays. They also reduced levels of intracellular cyclic adenosine monophosphate (cAMP) in a dose-dependent manner. Upon treatment of the cells with 100 µM concentrations of SY-15 and SY-17, there was a respective decrease in the intracellular cAMP levels by 63.43% and 53.83%. Subsequent computational analysis was conducted to elucidate the binding interactions of SY-15 and SY-17 with the α2A-AR. The binding free energies of SY-15 and SY-17 calculated by MD simulations were -45.93 and -71.97 kcal/mol. MD simulations also revealed that both compounds act as bitopic agonists, occupying the orthosteric site and a novel exosite of the receptor simultaneously. Our findings of integrative computational and experimental approaches could offer the potential to enhance ligand affinity and selectivity through dual-site occupancy and provide a novel direction for the rational design of sedatives and analgesics.

Role of electroanatomical mapping-guided superior vena cava isolation in paroxysmal atrial fibrillation patients without provoked superior vena cava triggers: a randomized controlled study.

AIMS: Data about whether empirical superior vena cava (SVC) isolation (SVCI) improves the success rate of paroxysmal atrial fibrillation (PAF) are conflicting. This study sought to first investigate the characteristics of SVC-triggered atrial fibrillation and secondly investigate the impact of electroanatomical mapping-guided SVCI, in addition to circumferential pulmonary vein isolation (CPVI), on the outcome of PAF ablation in the absence of provoked SVC triggers. METHODS AND RESULTS: A total of 130 patients undergoing PAF ablation underwent electrophysiological studies before ablation. In patients for whom SVC triggers were identified, SVCI was performed in addition to CPVI. Patients without provoked SVC triggers were randomized in a 1:1 ratio to CPVI plus SVCI or CPVI only. The primary endpoint was freedom from any documented atrial tachyarrhythmias lasting over 30 s after a 3-month blanking period without anti-arrhythmic drugs at 12 months after ablation. Superior vena cava triggers were identified in 30 (23.1%) patients with PAF. At 12 months, 93.3% of those with provoked SVC triggers who underwent CPVI plus SVCI were free from atrial tachyarrhythmias. In patients without provoked SVC triggers, SVCI, in addition to CPVI, did not increase freedom from atrial tachyarrhythmias (87.9 vs. 79.6%, log-rank P = 0.28). CONCLUSION: Electroanatomical mapping-guided SVCI, in addition to CPVI, did not increase the success rate of PAF ablation in patients who had no identifiable SVC triggers. REGISTRATION: ChineseClinicalTrials.gov: ChiCTR2000034532.

Study on the Hydrogen Effect and Interface/Border Traps of a Depletion-Mode AlGaN/GaN High-Electron-Mobility Transistor with a SiNx Gate Dielectric at Different Temperatures.

In this study, the electrical characteristics of depletion-mode AlGaN/GaN high-electron-mobility transistors (HEMTs) with a SiNx gate dielectric were tested under hydrogen exposure conditions. The experimental results are as follows: (1) After hydrogen treatment at room temperature, the threshold voltage VTH of the original device was positively shifted from -16.98 V to -11.53 V, and the positive bias of threshold was 5.45 V. When the VDS was swept from 0 to 1 V with VGS of 0 V, the IDS was reduced by 25% from 9.45 A to 7.08 A. (2) Another group of original devices with identical electrical performance, after the same duration of hydrogen treatment at 100 °C, exhibited a reverse shift in threshold voltage with a negative threshold shift of -0.91 V. The output characteristics were enhanced, and the saturation leakage current was increased. (3) The C-V method and the low-frequency noise method were used to investigate the effect of hydrogen effect on the device interface trap and border trap, respectively. It was found that high-temperature hydrogen conditions can passivate the interface/border traps of SiNx/AlGaN, reducing the density of interface/border traps and mitigating the trap capture effect. However, in the room-temperature hydrogen experiment, the concentration of interface/border traps increased. The research findings in this paper provide valuable references for the design and application of depletion-mode AlGaN/GaN HEMT devices.

Collision-attachment simulation of membrane fouling by oppositely and similarly charged colloids.

The fouling propensity of oppositely charged colloids (OCC) and similarly charged colloids (SCC) on reverse osmosis (RO) and nanofiltration (NF) membranes are systematically investigated using a developed collision-attachment approach. The probability of successful colloidal attachment (i.e., attachment efficiency) is modelled by Boltzmann energy distribution, which captures the critical roles of colloid-colloid/membrane interaction and permeate drag. Our simulations highlight the important effects of ionic strength Is, colloidal size dp and initial flux J0 on combined fouling. In a moderate condition (e.g., Is =10 mM, dp=50 nm and J0= 100 L/m2h), OCC mixtures shows more severe fouling compared to the respective single foulant owing to electrostatic neutralization. In contrast, the flux loss of SCC species falls between those of the two single foulants but more closely resembles that of the single low-charged colloids due to its weak electrostatic repulsion. Increased ionic strength Is leads to less severe fouling for OCC but more severe fouling for SCC, as a result of the suppressed electrostatic attraction/repulsion. At a high Is (e.g., 3-5 M), all the single and mixed systems show the identical pseudo-stable flux Js. Small colloidal size leads to the drag-controlled condition, where severe fouling occurs for both single and mixed foulants. On the contrary, better flux stability appears at greater dp for both individual and mixed species, thanks to the increasingly dominated role of energy barrier and thus lowered attachment efficiency. Furthermore, higher J0 above limiting flux exerts greater permeate drag, leading to elevated attachment efficiency, and thus more flux losses for both OCC and SCC. Our modelling gains deep insights into the role of energy barrier, permeate drag, and attachment efficiency in governing combined fouling, which provides crucial guidelines for fouling reduction in practical engineering.

Discovery of LAH-1 as potent c-Met inhibitor for the treatment of non-small cell lung cancer.

ABSTRCTDysregulated HGF/c-Met pathway has been implicated in multiple human cancers and has become an attractive target for cancer intervention. Herein, we report the discovery of N-(3-fluoro-4-((2-(3-hydroxyazetidine-1-carboxamido)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxamide (LAH-1), which demonstrated nanomolar MET kinase activity as well as desirable antiproliferative activity, especially against EBC-1 cells. Mechanism studies confirmed the effects of LAH-1 on modulation of HGF/c-Met pathway, induction of cell apoptosis, inhibition on colony formation as well as cell migration and invasion. In addition, LAH-1 also showed desirable in vitro ADME properties as well as acceptable in vivo PK parameters. The design, synthesis, and characterisation of LAH-1 are described herein.

Physical activity, sleep disorders, and type of work in the prevention of cognitive function decline in patients with hypertension.

BACKGROUND: Hypertensive patients are likelier to have cognitive function decline (CFD). This study aimed to explore physical activity level, sleep disorders, and type of work that influenced intervention effects on cognitive function decline in hypertensive patients and to establish a decision tree model to analyze their predictive significance on the incidence of CFD in hypertensive patients. METHODS: This cross-sectional study recruited patients with essential hypertension from several hospitals in Shandong Province from May 2022 to December 2022. Subject exclusion criteria included individuals diagnosed with congestive heart failure, valvular heart disease, cardiac surgery, hepatic and renal dysfunction, and malignancy. Recruitment is through multiple channels such as hospital medical and surgical outpatient clinics, wards, and health examination centers. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Moreover, we obtained information on the patients' type of work through a questionnaire and their level of physical activity through the International Physical Activity Questionnaire (IPAQ). RESULTS: The logistic regression analysis results indicate that sleep disorder is a significant risk factor for CFD in hypertension patients(OR:1.85, 95%CI:[1.16,2.94]), mental workers(OR:0.12, 95%CI: [0.04,0.37]) and those who perform both manual and mental workers(OR: 0.5, 95%CI: [0.29,0.86]) exhibit protective effects against CFD. Compared to low-intensity, moderate physical activity(OR: 0.53, 95%CI: [0.32,0.87]) and high-intensity physical activity(OR: 0.26, 95%CI: [0.12,0.58]) protects against CFD in hypertension patients. The importance of predictors in the decision tree model was ranked as follows: physical activity level (54%), type of work (27%), and sleep disorders (19%). The area under the ROC curves the decision tree model predicted was 0.72 [95% CI: 0.68 to 0.76]. CONCLUSION: Moderate and high-intensity physical activity may reduce the risk of developing CFD in hypertensive patients. Sleep disorders is a risk factor for CFD in hypertensive patients. Hypertensive patients who engage in mental work and high-intensity physical activity effectively mitigate the onset of CFD in hypertensive patients.

Improving antibody optimization ability of generative adversarial network through large language model.

Generative adversarial networks (GANs) have successfully generated functional protein sequences. However, traditional GANs often suffer from inherent randomness, resulting in a lower probability of obtaining desirable sequences. Due to the high cost of wet-lab experiments, the main goal of computer-aided antibody optimization is to identify high-quality candidate antibodies from a large range of possibilities, yet improving the ability of GANs to generate these desired antibodies is a challenge. In this study, we propose and evaluate a new GAN called the Language Model Guided Antibody Generative Adversarial Network (AbGAN-LMG). This GAN uses a language model as an input, harnessing such models' powerful representational capabilities to improve the GAN's generation of high-quality antibodies. We conducted a comprehensive evaluation of the antibody libraries and sequences generated by AbGAN-LMG for COVID-19 (SARS-CoV-2) and Middle East Respiratory Syndrome (MERS-CoV). Results indicate that AbGAN-LMG has learned the fundamental characteristics of antibodies and that it improved the diversity of the generated libraries. Additionally, when generating sequences using AZD-8895 as the target antibody for optimization, over 50% of the generated sequences exhibited better developability than AZD-8895 itself. Through molecular docking, we identified 70 antibodies that demonstrated higher affinity for the wild-type receptor-binding domain (RBD) of SARS-CoV-2 compared to AZD-8895. In conclusion, AbGAN-LMG demonstrates that language models used in conjunction with GANs can enable the generation of higher-quality libraries and candidate sequences, thereby improving the efficiency of antibody optimization. AbGAN-LMG is available at http://39.102.71.224:88/.

BioEGRE: a linguistic topology enhanced method for biomedical relation extraction based on BioELECTRA and graph pointer neural network.

BACKGROUND: Automatic and accurate extraction of diverse biomedical relations from literature is a crucial component of bio-medical text mining. Currently, stacking various classification networks on pre-trained language models to perform fine-tuning is a common framework to end-to-end solve the biomedical relation extraction (BioRE) problem. However, the sequence-based pre-trained language models underutilize the graphical topology of language to some extent. In addition, sequence-oriented deep neural networks have limitations in processing graphical features. RESULTS: In this paper, we propose a novel method for sentence-level BioRE task, BioEGRE (BioELECTRA and Graph pointer neural net-work for Relation Extraction), aimed at leveraging the linguistic topological features. First, the biomedical literature is preprocessed to retain sentences involving pre-defined entity pairs. Secondly, SciSpaCy is employed to conduct dependency parsing; sentences are modeled as graphs based on the parsing results; BioELECTRA is utilized to generate token-level representations, which are modeled as attributes of nodes in the sentence graphs; a graph pointer neural network layer is employed to select the most relevant multi-hop neighbors to optimize representations; a fully-connected neural network layer is employed to generate the sentence-level representation. Finally, the Softmax function is employed to calculate the probabilities. Our proposed method is evaluated on three BioRE tasks: a multi-class (CHEMPROT) and two binary tasks (GAD and EU-ADR). The results show that our method achieves F1-scores of 79.97% (CHEMPROT), 83.31% (GAD), and 83.51% (EU-ADR), surpassing the performance of existing state-of-the-art models. CONCLUSION: The experimental results on 3 biomedical benchmark datasets demonstrate the effectiveness and generalization of BioEGRE, which indicates that linguistic topology and a graph pointer neural network layer explicitly improve performance for BioRE tasks.

BERT2DAb: a pre-trained model for antibody representation based on amino acid sequences and 2D-structure.

Prior research has generated a vast amount of antibody sequences, which has allowed the pre-training of language models on amino acid sequences to improve the efficiency of antibody screening and optimization. However, compared to those for proteins, there are fewer pre-trained language models available for antibody sequences. Additionally, existing pre-trained models solely rely on embedding representations using amino acids or k-mers, which do not explicitly take into account the role of secondary structure features. Here, we present a new pre-trained model called BERT2DAb. This model incorporates secondary structure information based on self-attention to learn representations of antibody sequences. Our model achieves state-of-the-art performance on three downstream tasks, including two antigen-antibody binding classification tasks (precision: 85.15%/94.86%; recall:87.41%/86.15%) and one antigen-antibody complex mutation binding free energy prediction task (Pearson correlation coefficient: 0.77). Moreover, we propose a novel method to analyze the relationship between attention weights and contact states of pairs of subsequences in tertiary structures. This enhances the interpretability of BERT2DAb. Overall, our model demonstrates strong potential for improving antibody screening and design through downstream applications.

Quantifying the ecological carrying capacity of grasslands in Inner Mongolia.

Quantifying the ecological carrying capacity has emerged as a crucial factor for maintaining ecosystem stability for sustainable development in vulnerable eco-regions. Here, we propose a new framework for ecological carrying capacity quantification suitable for vulnerable eco-regions. We applied this framework to calculate the ecological carrying capacity of Inner Mongolia from 1987-2015 and used a geographical detector to identify the driving factors behind spatial heterogeneity. Our results revealed the following. (1) The above-ground net primary production (ANPP) required to support the ecosystem service of soil conservation (ANPPSC) decreased from northeast to southwest, whereas the distribution pattern of ANPP required to support the ecosystem service of sand fixation (ANPPSF) exhibited a contrary trend. The average annual ANPP required to support the ecosystem service of natural regeneration (ANPPNR) in Inner Mongolia from 1987 to 2015 was 101.27 gCm-2year-1, revealing a similar spatial distribution with ANPP. (2) The total ecological carrying capacity of Inner Mongolian grassland was 78.52 million sheep unit hm-2. The regions with insufficient provisioning service capability accounted for 4.18% of the total area, primarily concentrated in the east and northwest. (3) The average optimal livestock number for grasslands in Inner Mongolia was 1.59 sheep unit hm-2 from 1987-2015, ranging from 0.77 to 1.69 sheep unit hm-2 across different zones. The average ecological carrying capacity of the cold temperate humid, medium-temperate arid, and warm temperate semi-humid regions was less than 1.08 sheep unit m-2, suggesting a need to prohibit grazing in these areas. (4) The primary influencing factors affecting ecological carrying capacity distribution were normalized difference vegetation index (NDVI), precipitation, and soil type. The framework developed herein can help identify sustainable development potential from the ecosystem service perspective and effectively contribute to decision-making in grassland ecosystem management.

The role of perivascular adipose tissue-secreted adipocytokines in cardiovascular disease.

Perivascular adipose tissue and the vessel wall are connected through intricate bidirectional paracrine and vascular secretory signaling pathways. The secretion of inflammatory factors and oxidative products by the vessel wall in the diseased segment has the ability to influence the phenotype of perivascular adipocytes. Additionally, the secretion of adipokines by perivascular adipose tissue exacerbates the inflammatory response in the diseased vessel wall. Therefore, quantitative and qualitative studies of perivascular adipose tissue are of great value in the context of vascular inflammation and may provide a reference for the assessment of cardiovascular ischemic disease.

Heterometallic ZnHoMOF as a Dual-Responsive Luminescence Sensor for Efficient Detection of Hippuric Acid Biomarker and Nitrofuran Antibiotics.

Developing efficient and sensitive MOF-based luminescence sensors for bioactive molecule detection is of great significance and remains a challenge. Benefiting from favorable chemical and thermal stability, as well as excellent luminescence performance, a porous Zn(II)Ho(III) heterometallic-organic framework (ZnHoMOF) was selected here as a bifunctional luminescence sensor for the early diagnosis of a toluene exposure biomarker of hippuric acid (HA) through "turn-on" luminescence enhancing response and the daily monitoring of NFT/NFZ antibiotics through "turn-off" quenching effects in aqueous media with high sensitivity, acceptable selectivity, good anti-interference, exceptional recyclability performance, and low detection limits (LODs) of 0.7 ppm for HA, 0.04 ppm for NFT, and 0.05 ppm for NFZ. Moreover, the developed sensor was employed to quantify HA in diluted urine samples and NFT/NFZ in natural river water with satisfactory results. In addition, the sensing mechanisms of ZnHoMOF as a dual-response chemosensor in efficient detection of HA and NFT/NFZ antibiotics were conducted from the view of photo-induced electron transfer (PET), as well as inner filter effects (IFEs), with the help of time-dependent density functional theory (TD-DFT) and spectral overlap experiments.

Relating critical and limiting fluxes to metastable and long-term stable fluxes in colloidal membrane filtration through collision-attachment theory.

In membrane technology for water/wastewater treatment, the concepts of critical flux (JC) and limiting flux (JL) suggest the existence of a threshold flux below which no fouling occurs. However, their important roles on stable flux duration have not been sufficiently understood. This work adopts a collision-attachment approach to clarify the relationship of JC, JL to metastable (i.e., short-term stable) and long-term stable fluxes based on their dependence on initial flux (J0), foulant-clean-membrane energy barrier (Ef-m), and foulant-fouled-membrane energy barrier (Ef-f). When J0 is below JL, water flux remains stable over a long time even for the case of J0 over JC, thanks to the strongly repulsive Ef-f. At J0 > JL and J0 > JC, the water flux is unstable at the beginning of filtration, and the flux ultimately decreases to JL as the long-term stable flux. Under the condition of JL < J0 ≤ JC, an initial metastable flux appears owing to the high Ef-m, with longer metastable period observed at lower J0 and for more hydrophilic/charged membrane or colloids. Nevertheless, rapid flux decline occurs subsequently due to the energy barrier shifting to weak Ef-f, and the water flux eventually degenerates to JL in long-term fouling duration. Our results provide significant guidelines for fouling control strategies with respect to membrane design, feedwater pretreatment, and operational optimization.

Association between serum apolipoprotein A1 and atrial fibrillation in the Chinese population: a case-control study.

BACKGROUND: The relationship between serum apolipoprotein A1 (APOA1) and atrial fibrillation (AF) is not known. Therefore, we sought to investigate the associations between APOA1 and AF in the Chinese population. METHODS: This case-control study included 950 patients with AF (29-83 years old, 50.42% male) who were hospitalized consecutively in China between January 2019 and September 2021. Controls with sinus rhythm and without AF were matched (1:1) to cases by sex and age. Pearson correlation analysis was performed to investigate the correlation between APOA1 and blood lipid profiles. Multivariate regression models were used to explore the association between APOA1 and AF. The receiver operator characteristic (ROC) curve was constructed to examine the performance of APOA1. RESULTS: Multivariate regression analysis showed that low serum APOA1 in men and women with AF was significantly associated with AF (OR = 0.261, 95% CI: 0.162-0.422, P < 0.001). Pearson correlation analysis indicated that serum APOA1 was positively correlated with total cholesterol (TC) (r = 0.456, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = 0.825, p < 0.001), high-density lipoprotein cholesterol (HDL-C) (r = 0.238, p < 0.001), and apolipoprotein B (APOB) (r = 0.083, p = 0.011). ROC curve analysis showed that APOA1 levels of 1.105 g/L and 1.205 g/L were the optimal cut-off values for predicting AF in males and females, respectively. CONCLUSION: Low APOA1 in male and female patients is significantly associated with AF in the Chinese population of non-statin users. APOA1 may be a potential biomarker for AF and contribute to the pathological progression of AF along with low blood lipid profiles. Potential mechanisms remain to be further explored.

Half versus normal saline irrigation during catheter ablation of outflow tract ventricular arrhythmias (HALF): a multi-center, parallel, open-label, randomized controlled study.

BACKGROUND: Animal studies demonstrated that deeper lesions could be achieved during radio-frequency catheter ablation (RFCA) by using half saline (HS) compared to normal saline (NS) as irrigation. OBJECTIVES: This study sought to compare the efficiency and safety of HS and NS for irrigation during RFCA of idiopathic outflow tract ventricular arrhythmia (OT-VA). METHODS: In this multicenter, randomized controlled study, 167 patients undergoing RFCA of OT-VA were randomized 1:1 to receive HS- or NS-irrigated ablation. Acute success was defined as the absence of induced targeted premature ventricular contraction (PVC) at the end of the procedure. The 6-month success was defined as a ≥ 80% reduction of pre-procedural PVC burden. RESULTS: There were no differences of baseline characteristics between the HS and NS group. Patients in HS group had shorter total ablation time (259.5 ± 155.5 S vs. 355.6 ± 230.7 S, P = 0.04) than that in NS group. The acute and 6-month success rates were similar between the HS and NS group (92.8 vs. 91.7%, P = 0.79; 90.9 vs. 92.1%, P = 0.79, respectively). No significant difference was observed in the incidence of steam pops between the HS and NS group (2.4 vs. 1.2%, P = 0.62). CONCLUSIONS: The ablation using HS irrigation achieved similar success rate and safety compared to that using NS irrigation but was associated with a shorter total ablation time. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059205).

Multi-protocol exploratory treatment for metastatic castration-resistant prostate cancer with BRCA mutations: a case report and literature review.

Most patients with metastatic hormone sensitive prostate cancer will progress to metastatic castration-resistant prostate cancer (mCRPC); Finding a highly effective, safe treatment with low recurrence rate has important clinical implications. Herein, we present a case of a 65-year-old man with castration-resistant prostate cancer treated by multi-protocol exploration. Magnetic resonance imaging (MRI) revealed prostate cancer invading the bladder, seminal vesicle glands, and peritoneum with pelvic lymph node metastasis. Transrectal B ultrasound puncture of prostate tissue was performed, and the pathological diagnosis was prostatic adenocarcinoma. CTC (Circulating tumor cell) gene test was performed in peripheral blood, and the result showed BRCA1 gene mutation. The patient died of tumor complications after trying docetaxel combined with cisplatin chemotherapy, PARP inhibitor (nilaparib), PD-1 inhibitor (tislelizumab) and other treatments. This patient showed that the selection of an individualized combination chemotherapy regimen based on genetic testing results benefited the patient's tumor control. When choosing a treatment regimen, problems such as failure to respond to re-chemotherapy and resistance to nilaparib may lead to deterioration of the condition.