ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.

BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

AIM: To investigate the pharmacokinetic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS / MS. METHODS: An UPLC-MS / MS method was established to simultaneously detect tetrahydropalmatine, nobiletin and costunolide in the plasma and tissues of SD rats. The method was applied to investigate the pharmacokinetic characteristics and tissue distribution. RESULTS: After a single oral administration, the three active components were rapidly absorbed into the body, with a peak concentration (Cmax) of (13.73 ± 7.50), (27.01 ± 17.69) and (6.73 ± 29.94) ng / mL for tetrahydropalmatine, nobiletin, and costunolide, respectively. The time to reach the peak concentration (Tmax) was (1.40 ± 0.93), (0.63 ± 0.28) and (2.38 ± 8.81) h, respectively. The area under the curve (AUC) was (80.43±40.03), (41.30±28.69) and (303.90 ± 136.69) ng · h · mL

The application of artificial intelligence(AI)in medical diagnosis and treatment is becoming increasingly widespread,providing doctors and patients with more high-quality,efficient and personalized medical services.However,it also raised a series of ethical issues such as data security,algorithm transparency,responsibility definition,fairness and justice,doctor-patient relationships,and other aspects.Based on the combing of existing research results,this paper analyzed the research status of medical ethics in the application of AI in diagnosis and treatment,as well as expected that future medical ethics research can further explore the ethical issues of AI technology in medical treatment in greater depth,thus ensuring the rational application of AI in the medical field and maximizing the protection of patients'rights and interests.

Objectives:To explore the risk factors for death from ruptured acute aortic dissection during emergency treatment,construct and validate a risk prediction model for death from ruptured acute aortic dissection during emergency treatment. Methods:A total of 301 cases of acute aortic dissection patients who were admitted to Chinese Academy of Medical Sciences Fuwai Hospital from January 2018 to August 2021 were included in this study.Patients were divided into survival subgroup(n=239)and death subgroup(n=62)according to whether dissection rupture occurred in the acute stage of the disease.Univariate and multivariate analyses were performed.Logistic regression analysis was used to establish the risk prediction model.The Hosmer-Lemeshow test was conducted to assess the model's goodness of fit,and the receiver operating characteristic curve(ROC curve)was used to evaluate the model's predictive performance.A prospective validation was performed on 129 cases of acute aortic dissection patients admitted to our hospital's emergency department from September 2021 to September 2022. Results:Among the 301 cases of acute aortic dissection patients,there were 62 cases of rupture and death,with an incidence rate of 20.6%.The results of multivariate analysis showed that age(OR=1.066,95%CI:1.034-1.099),type A dissection(OR=0.045,95%CI:0.006-0.364),history of hypertension(OR=0.377,95%CI:0.167-0.850),and concomitant hypotension(OR=4.424,95%CI:1.467-13.340)were determinants of deaths.The model formula was Z=-5.624+0.064×age-0.976×history of hypertension(yes=1,no=0)-3.104×type(Type A=0,Type B=1)+1.487×concomitant hypotension(yes=1,no=0).The Hosmer-Lemeshow test result showed χ2=9.328,df=8,P=0.315,the area under the ROC curve was 0.874,sensitivity was 79.0%,specificity was 81.6%,and the maximum Youden index was 0.606.The model validation result showed that the area under the ROC curve was 0.722,sensitivity was 73.7%,specificity was 69.1%,and accuracy was 89.9%. Conclusions:Age,history of hypertension,dissection type,and combined hypotension are predictors of the risk prediction model for death from dissection rupture in patients with acute aortic dissection during emergency treatment.The model constructed in this study has good predictive performance,which can provide reference for medical staffto quickly identify high-risk patients for death from ruptured acute aortic dissection and timely predictive measures could be highlighted in indicated cases.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.

In recent years,radiation therapy has become a cornerstone in the treatment of head and neck tumors,significantly improving patient survival rates.However,the issue of radiation-induced carotid artery stenosis has garnered increasing attention.Characterized by multiple,long-segment,and unstable lesions,radiation-induced carotid stenosis presents unique challenges that traditional therapeutic approaches struggle to address.This review systematically summarized the pathological features and underlying mechanisms of radiation-induced carotid stenosis,with a focus on the roles of endothelial cells,smooth muscle cells,and vasa vasorum damage.Future research directions and preventive strategies are also discussed.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.