Voice biomarkers， as an emerging smart medical technology， are now being used in applications such as assisting in the diagnosis and treatment of diseases， facilitating accurate and personalized medical services for patients. However， it also raises many ethical issues， including informed consent， privacy protection， accuracy and reliability， data security， legal risks， and other issues. This paper systematically sorted out the ethical issues in the applications of voice biomarkers in the medical field， summarized these issues， such as informed consent， privacy protection， accuracy and reliability， data security， and legal risks， as well as explored the corresponding coping strategies. These countermeasures encompassed utilizing new media platforms to raise public awareness of voice biomarkers， strengthening supervision and management to promote the privacy protection of voice biomarkers， reducing algorithm biases to promote the general benefits of voice biomarkers to the public， establishing multidisciplinary teams to protect the data security of voice biomarkers， and encouraging medical professionals and researchers to participate in policy research， with a view to providing references for promoting and regulating the applications of voice biomarkers in the medical field.

ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

The existing epilepsy seizure detection algorithms have problems such as overfitting and poor generalization ability due to high reliance on manual labeling of electroencephalogram's data and data imbalance between seizure and interictal periods. An unsupervised learning detection method for epileptic seizure that jointed graph attention network (GAT) and Transformer framework (GAT-T) was proposed. In this method, channel correlations were adaptively learned by GAT encoder. Temporal information was captured by one-dimensional convolution decoder. Combining outputs of the two mentioned above, predicted values for electroencephalogram were generated. The collective anomaly score was calculated and the detection threshold was determined. The results demonstrated that GAT-T achieved the average performance exceeding 90% (or 99%) with a 0.25 s (or 2 s) time segment length, which could effectively detect epileptic seizures. Moreover, the channel association probability matrix was expected to assist clinicians in the initial screening of the epileptogenic zone, and ablation experiments also reflected the significance of each module in GAT-T. This study may assist clinicians in making more accurate diagnostic and therapeutic decisions for epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Algorithms ; Seizures/physiopathology* ; Neural Networks, Computer ; Signal Processing, Computer-Assisted

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Objective To investigate the relationship between serum high-mobility group box-1(HMGB-1)and glucose-regulated protein-78(GRP-78)levels and the severity of coronary artery lesions and myocardial fibrosis(MF)in patients with acute coronary syndrome(ACS).Methods A total of 155 ACS patients(ACS group)admitted to the hospital from January 2021 to August 2024 and 70 healthy volunteers who came to the hospital for health check ups during the same period(control group)were enrolled.ACS patients were further categorized based on the severity of coronary artery lesions(SYNTAX Ⅱ score)into mild lesion group(65 cases),moderate lesion group(51 cases),and severe lesion group(39 cases).Additionally,they were divided into the MF group(62 cases)and the non-MF group(93 cases)based on whether MF was present.Serum HMGB-1 and GRP-78 levels were measured using enzyme-linked immunosorbent assay.The correlation be-tween serum HMGB-1 and GRP-78 levels and SYNTAX Ⅱ score was assessed using Spearman's rank correla-tion.Multivariate Logistic regression analysis was used to identify factors influencing MF in ACS patients.Re-ceiver operating characteristic(ROC)curve was used to evaluate the value of serum HMGB-1 and GRP-78 levels in diagnosing severe coronary artery lesions and MF.Results Serum HMGB-1 and GRP-78 levels were significantly higher in the ACS group compared to the control group(P<0.05).The serum levels of HMGB-1 and GRP-78 increased sequentially in the mild,moderate,and severe lesion groups(P<0.05).Serum HMGB-1 and GRP-78 levels were positively correlated with SYNTAX Ⅱ score(P<0.05).Serum HMGB-1 and GRP-78 levels in the MF group were significantly higher than those in the non-MF group(P<0.05).High SYNTAX Ⅱ score,high N-terminal pro-brain natriuretic peptide,high HMGB-1,and high GRP-78 were independent risk factors for MF in ACS patients(P<0.05).The area under the curve for the combined detec-tion of serum HMGB-1 and GRP-78 levels for the diagnosis of severe coronary artery lesions in ACS patients was 0.887,which was larger than those of serum HMGB-1(0.803)and GRP-78(0.791)alone(P<0.05).The area under the curve of the combined detection of serum HMGB-1 and GRP-78 levels for the diagnosis of MF in ACS patients was 0.882,which was larger than those of serum HMGB-1(0.797)and GRP-78(0.789)alone(P<0.05).Conclusion Serum HMGB-1 and GRP-78 levels are elevated in ACS patients and are closely associated with the severity of coronary artery lesions and MF.The combined detection of serum HMGB-1 and GRP-78 levels has high value in diagnosing severe coronary artery lesions and MF in ACS patients.

In the past, aortic dissection, aortic aneurysm, and other aortic diseases, primarily rely on surgical intervention. In recent years, due to breakthroughs in materials science, endovascular therapy has become the first choice for the surgical treatment of most aortic diseases. However, traditional endovascular repair cannot fully meet the clinical needs for certain complex lesions involving the aortic arch and the originations of visceral arteries. The emergence of physician-modified stent technology has brought new hope for the treatment of complex aortic diseases. This article provides a detailed introduction to the concept, development, technical characteristics, and applications of physician-modified stents in the treatment of aortic diseases, analyzing their advantages and limitations. Physician-modified stents serve as a powerful complement to traditional endovascular interventions and commercial branched stents, yet further research and refinement are still required.

Objective This study aims to construct and evaluate a clinical decision support system for individualized frequency repositioning in ICU patients using big data and modern information technology,with the goal of improving ICU nursing quality.Methods From February to August 2023,a dedicated research team was established to construct a data model based on real-world data from 3,988 ICU patients,assessing the impact of different position change frequencies on the incidence of pressure injuries.Based on this model,a decision support system was designed and developed,incorporating modules for personalized patient characteristics input,data analysis and result queries,decision recording,and patient file management.From September to November 2023,ICU nurses at a tertiary hospital in Qingdao city was selected to use the system.A usability survey was conducted using the System Usability Scale(SUS)to evaluate the system's usability.Results The constructed decision support system can display the outcomes for patients under 7 different position change frequencies based on the input of personalized patient characteristics and the calculation results from the data model,providing precise decision support for nurses.A total of 85 nurses participated in the system usability evaluation,with the SUS score of 64.22±13.9.Conclusion The constructed individualized frequency of repositioning decision support system for ICU patients demonstrates good scientific validity and usability,providing clinical nurses with a valuable reference for implementing personalized position change frequencies for patients.

Hepatocellular carcinoma,as a com-mon malignant tumor,remains a serious global health problem.Traditional methods such as surgi-cal resection and chemotherapy have limited ef-fects in improving the prognosis of advanced hepa-tocellular carcinoma.With the deepening of re-search into molecular mechanisms,targeted thera-py has become an important direction for the treat-ment of hepatocellular carcinoma.In this review,we summarize the main targeted drugs and associ-ated therapeutic strategies for hepatocellular carci-noma,aiming to provide references and evidence for future related research.