Doctor digital twins， as a significant innovative form within the medical metaverse， integrate technologies such as large language models， natural language processing and multimodal learning. They can simulate doctors’ appearance， language style， and certain clinical reasoning， realizing diverse applications such as medical knowledge dissemination， intelligent consultation， health management， and medical education. While enhancing the accessibility and intelligence of healthcare services， doctor digital twins also give rise to multidimensional ethical challenges， such as data security and privacy breaches， algorithmic black box and bias， a crisis of doctor-patient trust， weakening of doctors’ subjectivity， and ambiguities in legal responsibility. This paper systematically reviewed the core concepts and current application status of doctor digital twins， constructing a tripartite analytical dimension centered on “technology， doctor-patient relationship， and law.” It focused on pivotal ethical issues encountered in practical application， including data security， patient informed consent and trust， legal responsibility delineation， and others. These aimed to provide ethical guidance and theoretical support for the sustainable development of doctor digital twins， promote the deep integration of smart healthcare and humanistic care， as well as contribute to building a safer， more trustworthy， and sustainable intelligent healthcare system.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

Objective To establish primary breast cancer cell lines from patient tissues and offer a new cancer cell model for basic research.Methods Breast cancer biopsy tissues were digested with typeⅡcollagenase and cultured in BCMI medium.When the cells proliferated rapidly,the medium was switched to DMEM.STR genotyping was per-formed to identify specific genetic markers of the four primary breast cancer cell lines.Colony expansion assays and sphere formation assays were conducted to analyze its tumorigenicity.Real-time PCR and Western blot experiments were used to analyze the expression of the epithelial-mesenchymal transition(EMT)molecule markers.Migration and invasion assays were performed to assess the metastatic potential of the primary breast cancer cells.Results We es?tablished four primary breast cancer cell lines:BC25#,BC51#,BC56#,and BC57#.These cell lines were cultured in DMEM medium,passaged multiple times and tagged with details about their clinical past.STR genotyping identified specific genetic markers for each of the four primary breast cancer cell lines.Clonogenic and sphere formation assays revealed that the four lines have a stronger tumor?forming capability compared to the classic breast cancer cell line T?47D.Real?time PCR and Western blot experiments showed that,compared to T?47D,the four primary breast cancer cell lines have decreased E?cadherin expression and increased vimentin expression.Migration and invasion assays indicated that BC25#had a higher metastatic potential than the traditional breast cancer cell line T?47D.Conclusions Four primary breast cancer cell lines,BC25#,BC51#,BC56#and BC57#are successfully estab?lished,which may act as new cancer cell model for laboratory research of breast cancer.

Objective To observe the efficacy of different pulse dose of ropivacaine combined with sufentanil for programmed intermittent epidural bolus(PIEB)infusion in labor analgesia and its impact on maternal and neonatal safety.Methods A total of 300 parturients undergoing labor anal-gesia were randomly divided into group A,group B,and group C,with 100 parturients in each group.The analgesic regimen consisted of 0.08％ropivacaine combined with 0.5 μg/mL sufentanil.The bolus infusion doses for groups A,B,and C were 6 mL,8 mL,and 10 mL,respectively,with a bolus interval of 40 min.The patient-controlled analgesia(PCA)dose was the same as the corre-sponding bolus dose,with a lockout time of 15 min.The medication was discontinued after fetal deliv-ery,with a limit dose of 30 mL/h.The Visual Analogue Scale(VAS)scores before analgesia(T0)and at 30 min(T1),1 h(T2),2 h(T3),3 h(T4)after analgesia,full dilation of the cervix(T5),and immediately after delivery(T6)were compared among groups.Additionally,the inci-dence of breakthrough pain,the first occurrence time of breakthrough pain,the rate of rescue analge-sia,the number of PCA pump presses,delivery outcomes,and neonatal conditions were compared.Results At each time points from T1 to T6,the VAS scores in all three groups were lower than that at T0,and were lower in groups B and C than those in group A(P＜0.05).However,there was no statistically significant difference in VAS scores between groups B and C(P＞0.05).The incidence of breakthrough pain,the rate of rescue analgesia,and the number of PC A pump presses were lower in the groups B and C than those in the group A,and the first occurrence time of breakthrough pain was later in groups B and C than those in group A(P＜0.05).There were no statistically signifi-cant differences among the three groups in neonatal birth weight,1-min and 5-min Apgar scores,neonatal behavioral neurological assessment(NBNA)scores,and the incidence of neonatal asphyxia(P＞0.05).Conclusion 0.08％ropivacaine combined with 0.5 μg/mL sufentanil for PIEB in labor analgesia is safe and effective,with a bolus dose of 8 mL achieving good analgesic effects and having minimal impact on both mothers and neonates.

To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience.

Objective To investigate the cellular characteristics in the development of retinal tumors induced by MY-CN overexpression,and to find the key proteins that play an important role in this process.Methods T-MYCN Y1 and Y2 cells cultured in vitro for 1 year and 2 years were selected for the experiment.The WERI-RB-1 cell line obtained from Shanghai Cell Bank of Chinese Academy of Sciences was taken as the mature retinoblastoma(RB)control(WERI-Rb-1 group).Untreated normal human retinal tissues were used as the control group.Cells were inoculated into a 24-well plate at a density of 1 × 104 cells per well,and the cell morphology was observed under a microscope and images were collected.Cell count was performed on the 4th,8th and 12th day after inoculation.Immunofluorescence staining was employed to de-tect the expression of the proliferation marker Ki67 and cone cell marker L/M opsin in each group.Quantitative real time polymerase chain reaction(qRT-PCR)was utilized to assess the expression of MYCN,CCNB1,CDK1,SYK,and RXRγ in cells across all groups.Proteomics analysis was performed to detect variations in protein expression profiles across groups and to identify key regulatory genes.Subsequently,cell growth and proliferation were evaluated after OTX2 knockdown by lentiviruses.Results The growth curve showed that there were(59.17±4.01)× 104 cells in the T-MYCN Y1 group,(85.14±4.54)× 104 cells in the T-MYCN Y2 group and(100.73±1.99)× 104 cells in the WERI-Rb-1 group on the 12th day of in-vitro culture(all P＜0.05).Compared with those in the control group,the positive cell rates of Ki67 and L/M opsin increased in T-MYCN Y1,T-MYCN Y2 and WERI-Rb-1 groups(all P＜0.001).The relative expression levels of MYCN mR-NAs in T-MYCN Y1,T-MYCN Y2 and WERI-Rb-1 groups were significantly higher than those in the control group(all P＜0.001).The relative expression levels of CCNB1 and CDK1 mRNAs also increased significantly in the three groups,com-pared with those in the control group(all P＜0.01).There was no significant difference in the relative expression of SYK mRNAs between T-MYCN Y1 and control groups(P＞0.05).The relative expression level of RXRγ mRNAs was significantly higher in the T-MYCN Y1 group than that in the control group(P＜0.05).The relative expression levels of SYK and RXRγmRNAs in T-MYCN Y2 and WERI-Rb-1 groups were significantly increased,compared with those in the control group(all P＜0.05).GO enrichment analysis showed that these differentially-expressed proteins were enriched into protein complex assembly and mitochondria pathways.KEGG enrichment analysis revealed that the enriched pathways of these differential-ly-expressed proteins included carbon metabolism,metabolic pathway and fatty acid degradation.Both proteomics and Western blot analyses indicated that OTX2 expression levels were the highest in the WERI-Rb-1 group,second highest in the T-MYCN Y2 group,and the lowest in the T-MYCN Y1 group(all P＜0.01).According to qRT-PCR,the expression levels of OTX2 mRNAs in T-MYCN Y1,T-MYCN Y2 and WRI-Rb-1 cells with OTX2 knockdown were lower than those in empty vec-tor controls(all P＜0.05).The growth curve of cells showed that after knocking down OTX2 in the three groups of cells,both cell growth and proliferation ability decreased significantly(all P＜0.001).Conclusion During the development of retinal tumors induced by MYCN overexpression,cells gradually exhibit characteristics similar to WERI-Rb-1 cells,which are a typical RB cell line.OTX2 plays an important role in MYCN amplification or the growth and proliferation of highly ex-pressed RB.Targeting OTX2 may become a new research direction for the treatment of RB.

Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new gener-ation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membrane-mediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP data-bases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

Objective To conduct a comprehensive evaluation of Amphotericin B Deoxycholate(AmB-D)for injection,Liposomal Amphotericin B(L-AmB)for injection,and Amphotericin B Colloidal Dispersion(ABCD)for injection,and to provide a reference for the selection and rational use of drugs in medical institutions.Methods Based on the quantitative evaluation and selection record form in the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),evidence was collected to conduct a comprehensive assessment of the included drugs.Results Comprehensively considering the pharmacological properties,efficacy,safety,economy,and other attributes of different preparations of amphotericin B,the quantitative scoring results were ranked from high to low,with ABCD(CSPC Ouyi Pharmaceutical Co.,Ltd.)scoring 79.10 points,L-AmB(Gilead Sciences)scoring 78.30 points,and L-AmB(Shanghai Shangyao Xinya Pharmaceutical Co.,Ltd.)scoring 72.01 points.AmB-D(Shanghai Shanghai Pharmaceutical Xinya Pharmaceutical Co.,Ltd)scored 63.20 points,and AmB-D(North China Pharmaceutical Co.,Ltd.)scored 59.78 points.Conclusion Both L-AmB and ABCD have better clinical efficacy and higher safety in the treatment of invasive fungal infections,and ABCD has a better price advantage than L-AmB.Based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),the evaluation results of different preparations of amphotericin B can provide a reference for the selection and rational use of amphotericin B in medical institutions.

Objective To compare functional differences of CD8+T cells in lung tissues between young and aged C57BL/6J mice during the contraction phase and memory immune response phase after infection with influenza A(H1N1)virus.Methods Lung tissues from young(3-month-old)and aged(24-month-old)C57BL/6J female mice without influenza virus infection were collected to prepare single-cell suspensions,which were stimulated with phorbol 12-myristate 13-acetate(PMA)/ionomycin or cluster of differentiation(CD)3/CD28 antibodies(T-cell antigen receptor/co-stimulatory signals)respectively(non-specific antigens stimulation).Flow cytometry intracellular cytokine staining(ICS)was performed on lung CD8+T cells to detect their secretion capacity of tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Young and aged C57BL/6J mice were infected intranasally with 490 PFU PR8 influenza virus,and reinfected with homologous influenza virus 28 days later.Lung tissues were isolated on day 28(the contraction phase)and day 32(the memory immune response phase)after primary infection.Influenza virus-specific MHC-Ⅰ tetramer staining was used to detect the proportion of virus-specific CD8+T cells in lung tissue CD8+T cells,and ICS was used to analyze TNF-α,IFN-γ,and granzyme B expression in CD8+CD44high T cell subset.Results After non-specific antigen stimulation,TNF-α and IFN-γ secretion capacity in lung tissue CD8+T cells of aged group mice was significantly higher than that of young group(P＜0.05).After virus-specific antigen stimulation,there were no statistically significant differences in the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B between the two groups of mice during the contraction phase(P＞0.05),while during the memory immune response phase,the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B in the aged group mice were significantly lower than those in the young group(P＜0.05).Conclusion CD8+T cells in aged mice maintain normal immune-related factor expression function under non-specific antigen stimulation,but show impaired immune-related factor expression function during antigen-specific memory immune response phase,suggesting that aging leads to defects in the formation or maintenance of CD8+T cell immune memory.