Closed-loop neuromodulation, especially using the phase of the electroencephalography (EEG) rhythm to assess the real-time brain state and optimize the brain stimulation process, is becoming a hot research topic. Because the EEG signal is non-stationary, the commonly used EEG phase-based prediction methods have large variances, which may reduce the accuracy of the phase prediction. In this study, we proposed a machine learning-based EEG phase prediction network, which we call EEG phase prediction network (EPN), to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data. We verified the performance of EPN on pre-recorded data, simulated EEG data, and a real-time experiment. Compared with widely used state-of-the-art models (optimized multi-layer filter architecture, auto-regress, and educated temporal prediction), EPN achieved the lowest variance and the greatest accuracy. Thus, the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Machine Learning ; Signal Processing, Computer-Assisted ; Male ; Adult ; Neural Networks, Computer ; Brain Waves/physiology*

Objective:To investigate the different expression levels of programmed cell death 1 ligand 1 (PD-L1) in non-small cell carcinoma (NSCLC) of distribution characteristics of TCM constitutions and prognosis.Methods:The clinical data of 355 NSCLC patients who had been treated with immune checkpoint inhibitors (ICIs) from January 2019 to June 2023 in the Cancer Medical Center of the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed, and their TCM constitutions were determined. According to the expression level of PD-L1, they were divided into three groups: low expression group (TPS≤1%), medium expression group (1% < TPS < 49%) and high expression group (TPS≥50%). Overall survival (OS) of patients was followed up, and the median OS were compared. Kaplan-Meier method was used to draw survival curves, and Log-rank test was used to compare the difference of survival curves. The independent risk factors of OS were analyzed by COX regression.Results:The distribution of different TCM constitutions showed statistical significance across the three groups ( P<0.05). The median OS for the medium and high expression groups were 21.082 months and 25.714 months, respectively, both significantly higher than the 14.437 months for the low expression group ( P<0.05). The survival curve of TCM constitutions showed that the constitutions significantly correlated with the prognosis of ICIs treatment were qi deficiency, phlegm dampness, and blood stasis ( P<0.05 or P<0.01). The median OS from high to low was 44.971 months for phlegm-dampness constitution, 23.297 months for qi-deficiency constitution, and 11.763 months for blood-stasis constitution. COX regression analysis indicated that medium PD-L1 expression ( HR=0.622, 95% CI=0.459,0.844, P=0.002), high PD-L1 expression ( HR=0.509, 95% CI=0.361,0.718, P<0.001), phlegm-dampness constitution ( HR=0.556, 95% CI=0.335,0.924, P=0.024), and blood-stasis constitution ( HR=2.952, 95% CI=1.929,4.518, P<0.001) were independent prognostic factors. Conclusions:The higher the expression level of PD-L1 in NSCLC patients, the better the prognosis of ICIs treatment. The prognosis of ICIs treatment is better for people with phlegm-dampness constitution and poor for those with blood stasis constitution.

ObjectiveTo analyze the temporal distribution characteristics of crisis calls and eight major counseling issues to the Shanghai mental health hotline, and to provide recommendations for improving hotline management. MethodsDescriptive statistics were used to analyze 1 106 crisis calls and the calls of eight major counseling issues to the Shanghai mental health hotline across months, time periods and weeks from October 2021 to September 2023, and the chi-square test was used to analyze whether there was any difference in the distribution of 1 106 crisis calls and the calls of eight major counseling issues across months, time periods and weeks. ResultsThere were significant differences in the number of crises calls across different months (χ²=87.816, P<0.05), time periods (χ²=161.848, P<0.05), and weekly distributions (χ²=63.329, P<0.05). The highest number of calls occurred in September, while January had the lowest. The peak call times were between 18:00‒20:00, with the fewest calls occurring between 3:00‒5:00. The day of the week with the highest number of calls was Saturday, while Wednesday had the lowest. Among the different types of counselling issues in crisis calls, the highest number of calls were related to mental disorders, while the fewest calls were related to COVID-19. ConclusionCrisis calls to the Shanghai mental health hotline are concentrated at specific times, indicating that relevant organizations should optimize resource allocation based on this time distribution.

Objective To observe the value of 5.0T MRI in measuring the volumes of hippocampal formation(HF)subfields in healthy adults.Methods Cranial high-resolution TIWI were prospectively obtained in 23 healthy adult volunteers using 5.0T and 3.0T MR scanners,respectively.HF was divided into 38 subfields,and then the volume of each subfield was measured using FreeSurfer software.The volumes of HF subfield based on 5.0T and 3.0T MR T1WI were compared,and the correlations of the outcomes were analyzed.Results Significant differences of the volumes of bilateral hippocampal tails,left parasubiculum,left molecular layer of hippocampal head,left granular cell-molecular layer-dentate gyrus head,right granular cell-molecular layer-dentate gyrus body,left cornu Ammonis(CA)1 head,left CA3 head,left CA4 head,right fimbria of hippocampus and left hippocampus amygdala transition area were found between 5.0T and 3.0T T1WI(all P＜0.05).The volumes of HF subfields measured based on 5.0T and 3.0T T1WI were moderately to highly positively correlated(all r＞0.5,all P＜0.01).Conclusion 5.0T MRI could be used to measure the volume of HF subfield in adults.

Objective To observe the consistency of 5.0T and 1.5T MR spectroscopy(MRS)for quantitating proton density fat fraction(PDFF)of liver.Methods Lipid emulsion models with lipid content of 0,5％,10％,15％,20％,25％and 30％were prepared.1H-MRS were collected using 5.0T and 1.5T MR scanners,respectively,and PDFF were obtained with jMRUI software.Totally 23 people,including 11 cases of fatty liver and 12 healthy adults were prospectively collected,and volume of interest(VOI)in the liver were selected to acquire 1H-MRS,and PDFF were obtained with jMRUI software and corresponding workstation,respectively.The consistencies of PDFF measured with different methods were analyzed.Results PDFF of lipid emulsion models with lipid content of 0,5％,10％,15％,20％,25％and 30％measured with jMRUI software and workstations based on 5.0T and 1.5T 1H-MRS all had good consistencies and being positively correlated,so were PDFF of liver tissue measured with jMRUI software and workstations based on 5.0T and 1.5T 1H-MRS.Conclusion 5.0T and 1.5T 1H-MRS had good consistency for quantitating liver PDFF.Measuring liver PDFF with workstation in clinical practice was helpful to simplifying workflow.

BACKGROUND: Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGFb1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. METHODS: An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. RESULTS: Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and a-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-b1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of profibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. CONCLUSION Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.

Abstract OBJECTIVE To analyze the drug-drug interaction during the use and treatment of nirmatrelvir/ritonavir tablets in children, and to provide reference for rational drug use in clinical practice. METHODS All hospitalized pediatric patients with using nirmatrelvir/ritonavir tablets from December 23, 2022 to February 8, 2023 in Children's Hospital, Zhejiang University School of Medicine were collected. The use of nirmatrelvir/ritonavir was analyzed, and the combination drugs were classified. The potential clinical drug-drug interactions of nirmatrelvir/ritonavir were analyzed through micromedex drug interaction database and the severity was graded. RESULTS A total of 48 patients using nirmatrelvir/ritonavir tablets were collected, with a median age of 6.71 years old(87 d-17.75 years old). The usage departments were mainly in the departments of hematology, ICU, infectious disease, and general internal medicine, and the main underlying disease being tumors. The median fever-reducing time after medication was 3 d. Many drugs were combined during medication period. A total of 15 potential drug-drug interaction drugs of nirmatrelvir/ritonavir tablets were collected, and potential drug interaction with antifungals should be considered. CONCLUSION The department with more usage of nirmatrelvir/ritonavir tablets in children is hematology, and the main underlying disease is tumors. When nirmatrelvir/ritonavir tablets are used in combination with potential drug-drug interaction drugs, attention should be paid to monitoring the efficacy and adverse reactions.

Objective : By testing the tensile strength of the poly(vinyl alcohol) (PVA)/bacterial cellulose(BC) composite membrane and its effect on the proliferation of mouse embryonic fibroblasts, its potential as new bone tissue engineering membrane were studied. Methods : PVA⁃BC films of different proportions and pure PVA films were prepared by self⁃evaporation method. The tensile strength of each group was tested. The group with the highest tensile strength was immersed in deionized water for 0. 5 h to measure its wet tensile strength. The microstructure of pure PVA film and the film with the highest tensile strength was observed by scanning electron microscopy (SEM) .X⁃ray diffraction and Fourier transform infrared ( FTIR) spectroscopy were used to analyze pure PVA, pure BC,and the film with the highest tensile strength respectively. Cell counting kit⁃8 (CCK⁃8) was applied to detect the survival rate in the blank control group, the pure PVA film group, and the composite film group with the highest tensile strength. Results : PVA⁃BC composite films were successfully prepared, X⁃ray diffraction and FTIR analysis revealed the co⁃presence of PVA and bacterial cellulose in the composite film. The initial tensile strength of the composite membrane increased with the BC ratio. When the concentration ratio of PVA to BC was 10 ∶ 7, the tensile strength reached (155. 5 ± 14. 7) MPa, and wet samples reached (13. 8 ± 1. 2) MPa. The CCK⁃8 test of NIH/3T3 showed that there was no significant difference among the PVA⁃BC composite film group, pure PVA group and blank control group after 1,4 and 7 days of cell culture ( P > 0. 05 ) . Conclusion PVA⁃BC film fabricated by blending method obtain certain mechanical properties and biocompatibility in both wet and dry states, which may be an appropriate candidate as a GBR membranes for clinical application.

Background::Epigenetics, and especially DNA methylation, contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). This study aimed to investigate the role of DNA methylation in SALS using whole blood of SALS patients.Methods::In total, 32 SALS patients and 32 healthy controls were enrolled in this study. DNA was isolated from whole blood collected from the participants. DNA methylation profiles were generated using Infinium MethylationEPIC BeadChip.Results::We identified 34 significant differentially methylated positions (DMPs) in whole blood from SALS patients, compared with the healthy controls. Of these DMPs, five were hypermethylated and 29 were hypomethylated; they corresponded to 13 genes. For the DMPs, ATAD3B and BLK were hypermethylated, whereas DDO, IQCE, ABCB1, DNAH9, FIGN, NRP1, TMEM87B, CCSAP, ST6GALNAC5, MYOM2, and RUSC1-AS1 were hypomethylated. We also identified 12 differentially methylated regions (DMRs), related to 12 genes (NWD1, LDHD, CIS, IQCE, TNF, PDE1C, LGALS1, CSNK1E, LRRC23, ENO2, ELOVL2, and ELOVL2-AS1). According to data from the Kyoto Encyclopedia of Genes and Genomes database, DNAH9 and TNF are involved in the amyotrophic lateral sclerosis (ALS) pathway. Correlation analysis between clinical features and DNA methylation profiling indicated that the methylation level of ELOVL2 and ARID1B was positively associated with the age of onset ( r = 0.86, adjust P = 0.001) and disease duration ( r = 0.83, adjust P = 0.01), respectively. Conclusions::We found aberrant methylation in DMP- and DMR-related genes, implying that many epigenetic alterations, such as the hypomethylation of DNAH9 and TNF, play important roles in ALS etiology. These findings can be helpful for developing new therapeutic interventions.