BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

ObjectiveTo investigate the disruptive effects of perinatal exposure to the environmental endocrine disruptor bisphenol AF (BPAF) on hepatic lipid metabolism in prepubertal (postnatal day 21, PND21) male offspring rats, and to provide scientific evidence for assessing the obesogenic effect of BPAF. MethodsSprague-Dawley (SD) rats aged 8 weeks were used in this study. Pregnant rats were divided into BPAF dose groups (2, 10, 50 mg·kg⁻¹) and a vehicle control group (corn oil), with 6 confirmed pregnant females per group. Gavage administration started from gestational day 0 and continued until the end of lactation. At PND21, one male offspring per litter was randomly selected. Serum concentrations of glucose (GLU), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), leptin (LEP), free fatty acid (FFA), as well as oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA), were measured. Pathological changes in liver and adipose tissues were evaluated, and the expression levels of genes related to hepatic lipid metabolism were measured. ResultsCompared to the vehicle control group, the 50 mg·kg⁻¹ group showed significantly increased serum LEP and MDA levels in male offspring (P<0.05), and significant upregulation of hepatic lipoprotein lipase (Lpl), fatty acid synthetase (Fas), and peroxisome proliferator-activated receptor γ (Pparg) gene expression (P<0.05). The 2 mg·kg⁻¹ group exhibited a significant increase in adipocyte length (P<0.05), while the 50 mg·kg⁻¹ group showed significant increases in both adipocyte area and length (P<0.05). No significant abnormalities were observed in liver histopathological examination. ConclusionPerinatal exposure to 50 mg·kg⁻¹ BPAF induced adipocyte hypertrophy, elevated leptin levels, upregulation of lipid synthesis gene expression, and enhanced oxidative stress in prepubertal male offspring, suggesting that BPAF may exert environmental obesogenic effects by disrupting lipid metabolism pathways.

Hepatitis D is an inflammatory liver disease caused by hepatitis D virus （HDV） infection， and co-infection of HDV and hepatitis B virus dramatically accelerates the progression of liver disease and significantly increases the risk of liver cirrhosis and hepatocellular carcinoma. However， due to insufficient awareness and concern about hepatitis D among the public， clinicians， and public health workers， the screening rate of hepatitis D remains at a relatively low level around the world. The true disease burden of hepatitis D has been seriously underestimated， and it has become one of the major challenges in the global campaign of hepatitis elimination. This article systematically reviews the current epidemiological situation of hepatitis D， prevention and control strategies， and related issues and challenges and analyzes the future strategies and measures for prevention and control， in order to provide a reference for promoting the achievement of the goal to eliminate viral hepatitis as a public health threat.

Hepatitis D virus （HDV）， as a defective virus， relies on the envelope protein of hepatitis B virus （HBV） to complete replication and transmission. Chronic hepatitis B （CHB） patients comorbid with HDV infection may experience significant acceleration of liver disease progression and a significantly higher risk of serious complications such as liver cirrhosis and hepatocellular carcinoma （HCC） compared with the patients with CHB alone， which poses a serious threat to the life and health of patients. At present， the coverage rate of HDV screening needs to be improved， and some patients with HBV/HDV co-infection have not been found in time. Therefore， strengthening the understanding of HDV among clinicians， expanding the scope of HDV screening， identifying patients with infection in a timely manner， and performing standardized antiviral therapy and long-term follow-up management are of great significance for improving the prognosis of patients， reducing disease burden， improving the quality of life of patients， and achieving the global goal of “eliminating viral hepatitis as a public health threat by 2030”.

OBJECTIVE To analyze the distribution characteristics of mirtazapine steady-state trough concentration and concentration-to-dose ratio （ C / D ）， and to investigate the influence of clinical and genetic factors on C / D . METHODS A retrospective study was conducted on hospitalized patients with depression who received mirtazapine treatment and underwent therapeutic drug monitoring at the First Hospital of Hebei Medical University from May 2022 to May 2025. The collected data included patients’ gender， age， body mass index， daily dose， steady-state trough concentration， smoking status， history of liver disease， drug type， concomitant medications， and CYP2D6 metabolic phenotype. The C / D was calculated. Spearman rank correlation was used to analyze the relationship between mirtazapine steady-state trough concentration and daily dose. Univariate analysis and multiple linear regression model were employed to screen the factors potentially influencing the C / D of mirtazapine. RESULTS A total of 226 patients were included. The daily dose of mirtazapine was 25.00 （24.82， 30.00） mg/d， the steady-state trough concentration was 44.46 （20.00， 70.00） ng/mL， and the C / D was 1.83 （1.00， 2.00） （ng·d）/（mL·mg）. Steady-state trough concentrations were within the reference range （30-80 ng/mL） in 121 patients （53.54%）， below the lower limit in 80 patients （35.40%）， and above the upper limit in 25 patients （11.06%）. A positive correlation was observed between mirtazapine steady-state trough concentration and daily dose （coefficient of determination was 0.320 8， P ＜0.001）. Gender， smoking status， and CYP2D6 metabolic phenotype were significantly associated with the mirtazapine C / D （ P ＜0.05）. CONCLUSIONS Significant interindividual variability exists in mirtazapine steady-state trough concentrations. Gender， smoking status， and CYP2D6 metabolic phenotype are identified as independent influencing factors for the mirtazapine C / D ， with higher C / D ratios observed in females， non-smokers， and intermediate metabolizers.

OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources， including national and local pharmaceutical administration policies， clinical practice guidelines/consensus， hospital information systems data， and genetic testing results， were integrated. Adhering to the principles of structure， standardization and dynamic updating， a knowledge base covering chemotherapeutic， targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed， and a closed-loop prescription review system was successfully established， encompassing pre-prescription real-time intervention， in-process interactive review， and post-prescription evaluation and analysis. From 2021 to 2024， the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions， 22 577 alerts were generated， with Cisplatin for injection （lyophilized） being the most frequently alerted drug （13 445 alerts）， and “ototoxicity risk due to combined use” alerts remained high （7 682 alerts）. For methotrexate-containing prescriptions， 3 721 alerts were recorded， primarily related to “precaution-related issues” （76.4%， 2 843/3 721）. For doxorubicin-containing prescriptions， 17 301 alerts were triggered， primarily related to “dosage and administration” （14 315 alerts）. For human epidermal growth factor receptor 2-targeted agents-containing prescriptions， 1 007 alerts were issued， mostly related to “reimbursement restrictions” （956 alerts）. For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions， the alerts increased year by year， totaling 13 273 alerts， primarily related to “inappropriate indication” （9 118 alerts）. Over the 4 years， the physician response rates to system alerts were 21.4%， 27.1%， 33.5% and 51.6%， respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review， encompassing a closed-loop process of “real-time pre-event intervention， interactive in-event prescription review， post-event evaluation and analysis”， has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital， where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally， the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.

ObjectiveTo investigate the effectiveness of teaching pedagogy based on outcome-based education (OBE) and conceive-design-implement-operate (CDIO) model in the teaching of exercise rehabilitation training. MethodsTwenty-seven postgraduate students majoring in exercise rehabilitation training of grade 2024 at Capital University of Physical Education and Sports were randomly divided into control group (n = 13) and experimental group (n = 14). The control group received routine teaching methods, while the experimental group received teaching of OBE-CDIO. After the course, theoretical scores, objective structured clinical examination (OSCE) scores and teaching satisfaction via questionnaire were compared between two groups. ResultsAfter the course, there was no significant difference in theoretical scores between two groups (t = 1.103, P > 0.05). Scores in all stations of OSCE were higher in the experimental group than in the control group (t > 2.181, P < 0.05), as well as the satisfaction scores of learning, enthusiasm, organization, group interaction, individual affinity, workload and examination (|t| > 3.781, P < 0.001). ConclusionThe teaching pedagogy based on the OBE-CDIO model can improve practical competence and teaching satisfaction among postgraduate students majoring in exercise rehabilitation training.

ObjectiveTo explore the training path of rehabilitation therapy professionals in local colleges and universities under the background of New Medicine. MethodsTaking Jining Medical University as an example, combining the interdisciplinary integration, intelligent driving and people-oriented New Medicine attributes of rehabilitation therapy, this study focused on the current practical problems in rehabilitation education, accurately aligned with the requirements of new medicine construction, reshaped the curriculum system with new concepts, empowered practical innovation with new technologies, and cultivated humanistic literacy with new connotations. By deeply integrating digital construction with educational practice, it carried out the construction and practice of the New Medicine talent training model in rehabilitation therapy, helping students form a stereoscopic knowledge structure, possess the ability to apply intelligent rehabilitation technology and solve complex rehabilitation problems, and become high-quality rehabilitation therapy talents with both morality and ability. ResultsThe overall construction of the rehabilitation therapy major established a model of Dual fusion foundation, Three element empowerment and Three dimensional soul casting, including reform and innovation in curriculum system, practical mode and moral education mechanism. It has formed a health oriented "vertical and horizontal integration-discipline fusion" dual-fusion stereoscopic curriculum system, an intelligent led "theory and practice-science and education-industry and education" three element integration practical mode, and a confucian medical culture "curriculum-practice-evaluation" three-dimensional integrated moral education mechanism. Through practical testing, this model achieved significant results and was widely recognized, including a significant improvement in the quality of talent cultivation, prominent achievements in resource construction, and prominent achievements in health services, providing strong support for the construction of regional rehabilitation medical systems. ConclusionThe reform of the rehabilitation treatment talent training model at Jining Medical University under the background of New Medicine provides a replicable and promotable practical paradigm for the training of rehabilitation talents in similar universities through reshaping the curriculum system, strengthening practical innovation, and cultivating humanistic literacy.

The negative “second childhood” theory in the West has raised the medical ethical issues of infantilizing elderly patients with Alzheimer’s disease. In contrast， Chinese classical childlike thought represents a positive and simple idea of the overall life course， which contains four core connotations， including seemingly weak yet resilient， returning to simplicity and being gifted with nature， purity without hypocrisy and sincere feelings， and enjoying playfulness while hating restraint. Drawing on the essence of Chinese classical childlike thought， learning from the past to guide the present， and fully exploring its ethical implications in contemporary Alzheimer’s disease care， can help overcome the stigma of the disease and establish a positive bioethics value in the whole society； help caregivers adjust their mindsets and optimize nursing ethics； help build a care approach that returns to nature and enhance patients’ physical and mental health； help create a game-oriented rehabilitation environment to help patients regain their happiness； and help promote emotional communication between doctors and patients and explore new methods of emotional healing. The classical childlike thought provides a novel approach to building a friendly society for Alzheimer’s disease in China and offers Chinese wisdom and solutions for the global care and treatment of Alzheimer’s disease.

Thomas Percival published the first edition of Medical Ethics in 1803 and is often regarded as the founder of modern medical ethics. After settling in Manchester in 1767， he established a reputation locally through his outstanding medical research and clinical work， contributions to public health affairs， and influence of his ethical works. In 1788， when a dispute arose among the medical staff at the Manchester Infirmary， Percival， as the hospital’s extraordinary physician and a highly respected figure in the region’s medical community， was commissioned to draft a code of conduct for medical staff. Taking this opportunity， he completed and published the book named Medical Ethics， which subsequently exerted a profound impact on the professional norms of physicians in the United Kingdom and the United States.