Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

The accurate prediction of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties represents a crucial step in early drug development for reducing failure risk. Current deep learning approaches face challenges with data sparsity and information loss due to single-molecule representation limitations and isolated predictive tasks. This research proposes molecular properties prediction with parallel-view and collaborative learning (MolP-PC), a multi-view fusion and multi-task deep learning framework that integrates 1D molecular fingerprints (MFs), 2D molecular graphs, and 3D geometric representations, incorporating an attention-gated fusion mechanism and multi-task adaptive learning strategy for precise ADMET property predictions. Experimental results demonstrate that MolP-PC achieves optimal performance in 27 of 54 tasks, with its multi-task learning (MTL) mechanism significantly enhancing predictive performance on small-scale datasets and surpassing single-task models in 41 of 54 tasks. Additional ablation studies and interpretability analyses confirm the significance of multi-view fusion in capturing multi-dimensional molecular information and enhancing model generalization. A case study examining the anticancer compound Oroxylin A demonstrates MolP-PC's effective generalization in predicting key pharmacokinetic parameters such as half-life (T0.5) and clearance (CL), indicating its practical utility in drug modeling. However, the model exhibits a tendency to underestimate volume of distribution (VD), indicating potential for improvement in analyzing compounds with high tissue distribution. This study presents an efficient and interpretable approach for ADMET property prediction, establishing a novel framework for molecular optimization and risk assessment in drug development.
Deep Learning

Objective To analyze the in-hospital and long term prognosis of acute myocardial infarction(AMI)patients with N-terminal B-type brain natriuretic peptide(NT-proBNP)peak value exceeding the up-per limit.Methods A total of 669 patients with AMI diagnosed in a hospital from 2013 to 2018 were selected as research objects.According to the peak value level of NT-proBNP,they were divided into the NT-proBNP peak value exceeding the upper limit group(50 cases)and the NT-proBNP peak value detectable group(619 cases).Propensity score was used for matching(1:2),and the patients were divided into NT-proBNP peak value exceeding the upper limit group(50 cases)and NT-proBNP peak value detectable group(107 cases),and the in-hospital prognosis and long-term prognosis of the two groups were compared,as well as the echo-cardiographic indexes of each group in the acute stage and recovery stage of AMI.Multiple linear regression a-nalysis was used to predict the factors affecting left ventricular ejection fraction in the recovery stage of AMI.Results After matching the propensity score,compared with the NT-proBNP peak value detectable group,the neutrophil to lymphocyte ratio,hypersensitive C reactive protein level and fibrinogen level in the NT-proBNP peak value exceeding the upper limit group were higher at admission,and the differences were statistically sig-nificant(P＜0.05).The proportion of Killip≥ Grade Ⅱ,left ventricular ejection fraction,hospitalization time and major adverse cardiovascular and cerebrovascular events in the NT-proBNP peak value exceeding the up-per limit group were compared with those in the NT-proBNP peak value detectable group,and the differences were statistically significant(P＜0.05).The left ventricular ejection fraction and left ventricular shortening fraction of the NT-proBNP peak value detection group in AMI acute stage were higher than those in the NT-proBNP peak value exceeding the upper limit group in AMI acute stage,and the difference was statistically significant(P＜0.05).Multiple linear regression analysis showed the relationship between the NT-proBNP peak value during hospitalization and the left ventricular ejection fraction of cardiac function during AMI re-covery.The results suggested that the NT-proBNP peak value was not a risk factor affecting the left ventricu-lar ejection fraction of cardiac function during AMI recovery.Conclusion AMI patients with NT-proBNP peak value exceeding the upper limit should be treated with a series of comprehensive treatment strategies to pro-mote their rehabilitation and improve their long-term prognosis.

Objective:To establish of a newmethod:for the rapid detection of H5N1-Avian Influenza virus by combining reverse transcription (RT), multiple cross displacement amplification (MCDA) and nanoparticle-based lateral flow biosensor (LFB).Methods:MCDA primers were designed based on gene sequences specific to Hemagglutinin (HA) and Neuraminidase (NA) in H5N1 avian influenza virus. The target genes HA and NA were amplified through reverse transcription and MCDA in one reaction system. Results were displayed by LFB. The assay was named as H5N1-mRT-MCDA-LFB. The reaction conditions of the H5N1-RT-MCDA-LFB method were optimized, and the sensitivity and specificity were also assessed.Results:The H5N1-RT-MCDA-LFB assay could achieve good amplification effect at a constant temperature of 65 ℃ for 40 minutes. The method had a lower limit of detection of 100 fg per reaction with 100-fold higher sensitivity than that of the RT-qPCR (lower limit of detection 10 pg per reaction). The assay was negative in detecting 28 common viruses, mycoplasmas, chlamydias, bacterias and funguses, except for H5N1. In addition, the H5N1-RT-MCDA-LFB method showed better validation in simulated clinical samples with a lower limit of detection at 1×10 2 copies/ml. Conclusion:The H5N1-RT-MCDA-LFB assay is a valuable molecular diagnostic technique for detecting H5N1 avian influenza virus due to its simplicity, rapidity, sensitivity and specificity.

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease with complex and diverse pathogenesis， and there is no effective treatment or specific drugs for its clinical treatment. In recent years， its incidence has been on the rise， and it has become the earnest expectation of medical researchers in China and abroad that related patients could be treated. AMP-activated protein kinase （AMPK） functions to regulate cellular energy homeostasis and mitochondrial homeostasis. When activated， it has a good intervention effect on NAFLD progression with lipid metabolism disorders and mitochondrial homeostasis disorders. For NAFLD， the activation of AMPK can inhibit the production of new lipogenesis in the liver， promote the oxidation of fatty acids in the liver， and enhance the mitochondrial function of adipose tissues. As a key target of metabolic diseases， AMPK can also improve apoptosis， liver fibrosis， autophagy， and inflammation. Traditional Chinese medicine （TCM） is good at treating diseases from multiple targets and multiple pathways and is also commonly used in the treatment of chronic liver disease in clinical practice. A large number of in vitro and in vivo experimental studies on NAFLD have shown that TCM monomers have good prospects for the treatment of NAFLD through the AMPK signaling pathway， including glycosides， phenols， alkaloids， flavonoids， quinones， terpenoids， and lignans， which are natural activators of AMPK. This study reviewed the research progress on TCM monomers in regulating the AMPK pathway to prevent and treat NAFLD， providing a broader perspective for TCM treatment of NAFLD.

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

Epigenetic modification is closely related to the occurrence and development of tumors. It mainly regulates gene function and expression level through DNA methylation, histone modification, regulation of non-coding RNA and chromatin structure reconstruction. At present, epigenetic drugs have been gradually applied to the treatment of malignant tumors. Common drug types include: DNA methyltransferase inhibitors and histone deacetylase inhibitors. However, these drugs still have many shortcomings and a wide range of clinical applications need further research. Encouragingly, the epigenetic drugs in combination with various anti-tumor drugs have shown great application potential. In this paper, we summarized the development mechanism of epigenetics in malignant tumors and the progress of related drugs.

BACKGROUND: The incidence and mortality of lung cancer often rank first in all malignant tumors. DNA methylation, as one of epigenetics, often participates in the development and progression of tumors. CDO1 as a tumor suppressor gene always undergoes methylation changes early in tumor development. Therefore, this study aims to discuss the value of CDO1 methylation in the early diagnosis of lung cancer. METHODS: Peripheral blood samples were collected from tumor patients and healthy people. Detection of the methylation level of CDO1 in plasma by sulfite modification and quantitative real-time PCR. RESULTS: The level of gene methylation in peripheral blood of lung cancer patients was significantly higher than that of benign lung disease patients and healthy people. The methylation level of CDO1 was significantly different in the stratified comparison of gender, lymph node metastasis and tumor-node-metastasis (TNM) stage (P<0.05). The sensitivity and specificity of CDO1 were 52.2% and 78.6%, respectively. The overall accuracy of the diagnosis was significantly higher than that of the clinical tumor markers, and the sensitivity of CDO1 to stage I and II patients was the highest (40.8%, 47.1%). In addition, CDO1 could effectively increase the sensitivity of diagnosis in multiple joint examinations. CONCLUSIONS Detecting the methylation level of CDO1 has a potentially huge advantage for the early diagnosis of lung cancer.

Objective To examine the prevalence of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS),and to evaluate the relationship of OSA with inflammatory biomarkers in ACS patients.Methods Patients with ACS treated at Beijing Anzhen Hopital from June 2015 to May 2017 were enrolled.Subjects were evaluated for OSA by sleep study,and were divided into a normal-mild OSA group (Apnea Hypopnea Index,AHI ＜ 15 times/h) and a moderate-severe OSA group (AHI ≥ 15 times/h).Laboratory examination and sleep study were monitored to analyze the effects of OSA on biomarkers by LSD-t test,Mann-whitney U test,or Chi-square test.Correlation analysis was performed to analyze the association of OSA with high sensitivity C-reactive protein (hs-CRP) by Spearman correlation anaylsis.Results A cohort of 836 patients with ACS were enrolled including 408 patients in the normal-mild OSA group and 428 patients in the moderate-severe OSA group.The levels of leukocyte(x 109L) [7.78 (6.33,9.86) vs 7.29 (6.01,9.16),P=0.006],neutrophils(× 109L) [5.05 (3.84,7.23)vs 4.80 (3.74,6.66),P=0.044],monocytes(x 109L) [0.42 (0.33,0.54) vs 0.39 (0.31,0.51),P=0.033],hsCRP(mg/L) [3.18 (1.10,11.52) vs 1.78 (0.65,6.46),P＜0.01],fibrinogen(g/L) [3.17 (2.87,3.74) vs 2.97 (2.59,3.50),P=0.002],and uric acid(μmol/L) [360 (302,422) vs 341(283,407),P=0.006] in the moderatesevere OSA group were significant higher than those in the normal-mild OSA group.AHI (correlation coefficient=0.171,R2=0.020,P＜0.01),ODI (correlation coefficient =0.201,R2=0.027,P＜0.01),and TSaO2 ＜ 90％ (correlation coefficient =0.105,R2=0.005,P＜0.01) were positively correlated with hs-CRP;minimal SaO2 (correlation coefficient=-0.100,R2=0.001,P=0.008) and mean SaO2 (correlation coefficient =-0.127,R2=0.006,P＜0.01) were negatively correlated with hs-CRP.Conclusions For patients with ACS,the level of inflammatory markers in the moderate-severe OSA group is significantly higher than that in the normal-mild OSA group.Hs-CRP is significantly associated with the severity of OSA.Diagnosis and monitoring of OSA should be considered in ACS management in the future.