AIM: To investigate the distribution characteristics of pathogens in patients with post-traumatic infectious endophthalmitis(PTIE)and their relationship with serum levels of macrophage inflammatory protein 1α(MIP-1α), heat shock protein 70(HSP70), and soluble triggering receptor expressed on myeloid cells 1(sTREM-1).METHODS:A total of 157 patients with PTIE from the Handan City Eye Hospital(The Third Hospital of Handan)from May 2023 to May 2025 were selected as the study group. They were divided into a good prognosis group and a poor prognosis group based on their uncorrected visual acuity at discharge. Meanwhile, 157 patients with ocular trauma but without endophthalmitis during the same period were selected as control group 1, and 157 healthy volunteers who underwent physical examinations during the same period were selected as control group 2. Aqueous humor and vitreous fluid samples were collected from the study group to detect the distribution of pathogens. The levels of serum MIP-1α, HSP70, and sTREM-1 were measured using the enzyme-linked immunosorbent assay. Multivariate Logistic regression analysis was performed to identify risk factors for poor prognosis. The predictive value of serum MIP-1α, HSP70, and sTREM-1 levels for poor prognosis was evaluated using receiver operating characteristic(ROC)and decision curve analysis(DCA).RESULTS: The general data of the participants in the three groups was comparable. A total of 173 pathogens were detected in the 157 patients with PTIE, with Gram-positive bacteria being the predominant type. The levels of serum MIP-1α and sTREM-1 in the study group were higher than those in control groups 1 and 2, while the level of HSP70 was lower than those in control groups 1 and 2(all P<0.05). There were no significant differences in the levels of serum MIP-1α, HSP70, and sTREM-1 between control groups 1 and 2(all P>0.05). In the poor prognosis group, the time of wound suture was ≥24 h, the wound location was in zones II/III, the type of trauma was rupture, the proportion of rupture injuries, and the levels of serum C-reactive protein, MIP-1α, and sTREM-1 were higher than those in the good prognosis group, while the level of HSP70 was decreased(all P<0.001). Multivariate Logistic regression analysis showed that the time of wound suture, wound location, type of trauma, C-reactive protein, MIP-1α, HSP70, and sTREM-1 were risk factors for poor visual prognosis in patients with PTIE(all P<0.05). The ROC curve results showed that the combined prediction of serum MIP-1α, HSP70, and sTREM-1 for poor visual prognosis in PTIE patients had an AUC value of 0.965, which was significantly higher than that of individual predictions(ZMIP-1α, ZHSP70, ZsTREM-1=3.628, 4.705, 3.930, all P<0.05). Additionally, the DCA curve showed that the combined prediction had a higher net benefit rate than individual predictions in the high-risk threshold range of 0.03-0.97.CONCLUSION:Gram-positive bacteria are the predominant type of pathogenic bacteria in patients with PTIE, with elevated levels of serum MIP-1α and sTREM-1 and decreased levels of HSP70. The combined detection of these three factors has a high predictive efficacy for visual prognosis in patients.

Myocardial infarction （MI） and osteoporosis （OP）， as two prevalent metabolic diseases with high morbidity and mortality rates， are respectively characterized by cardiovascular system dysfunction and bone homeostasis imbalance， collectively posing significant global public health challenges. While clinically often considered as independent diseases， recent studies have revealed shared pathological mechanisms between the two. This study initiated its exploration from the traditional Chinese medicine concept of the "heart-bone" axis， systematically analyzing the correlation between MI and OP from perspectives including hemodynamics， neuroendocrinology， calcium homeostasis， inflammation and vascular injury， as well as hormone levels. By discussing the pathological mechanisms of "heart disease affecting the bones and bone disease affecting the heart"， the study also elucidated advancements in both Western and traditional Chinese medicine treatments. The goal is to provide novel insights and methodologies for the prevention and treatment of "heart-bone comorbidities"， thereby facilitating comprehensive management of cardiovascular and skeletal diseases.

Myocardial infarction （MI） and osteoporosis （OP）， as two prevalent metabolic diseases with high morbidity and mortality rates， are respectively characterized by cardiovascular system dysfunction and bone homeostasis imbalance， collectively posing significant global public health challenges. While clinically often considered as independent diseases， recent studies have revealed shared pathological mechanisms between the two. This study initiated its exploration from the traditional Chinese medicine concept of the "heart-bone" axis， systematically analyzing the correlation between MI and OP from perspectives including hemodynamics， neuroendocrinology， calcium homeostasis， inflammation and vascular injury， as well as hormone levels. By discussing the pathological mechanisms of "heart disease affecting the bones and bone disease affecting the heart"， the study also elucidated advancements in both Western and traditional Chinese medicine treatments. The goal is to provide novel insights and methodologies for the prevention and treatment of "heart-bone comorbidities"， thereby facilitating comprehensive management of cardiovascular and skeletal diseases.

Informed consent constitutes a fundamental ethical principle in medical practice. With the in-depth integration of generative artificial intelligence （AI） represented by Chat Generative Pre-trained Transformer （ChatGPT） with medicine， it has brought revolutionary development to traditional informed consent while also introducing new ethical challenges. ChatGPT offers features such as improving the readability of informed consent content， enhancing its comprehensiveness and accuracy， and increasing the convenience of obtaining informed consent. However， as the application of ChatGPT in informed consent is still in the exploratory stage， it is imperative to proactively and fully consider the accompanying ethical issues， such as information security， liability determination， transparency， and fairness. This paper conducted an ethical analysis on the challenges faced by generative AI， represented by ChatGPT， in the application of informed consent and proposed countermeasures， such as upholding free and fully informed consent， strengthening the balance of rights and obligations in informed consent， and establishing a transparent and fair supervision mechanism. The aim was to promote the ethically compliant， orderly， and controllable development of generative AI in the field of medical informed consent.

Malignant tumors are one of the major causes of death in the population. Owing to limited clinical treatments， susceptibility to drug resistance， and generally low cure rates of conventional therapies， new treatment strategies need to be explored. Compared with existing therapies， traditional Chinese medicine （TCM） has unique advantages， such as low side effects， in the treatment of malignant tumors. Ferroptosis is a recently characterized form of regulated cell death associated with iron metabolism imbalance， lipid peroxidation， antioxidant system malfunction and other aspects. Studies have shown that TCM regulates Fe³⁺， Fe²⁺， glutathione， glutathione peroxidase 4 and other substances related to ferroptosis， thereby affecting lipid peroxidation and antioxidant processes， and then inducing ferroptosis. Through these mechanisms， TCM plays a key role in inhibiting the growth and spread of tumor cells and is involved in multiple stages of malignant tumor progression. In this study， we systematically retrieved the literature indexed in PbuMed and China National Knowledge Infrastructure （CNKI） with the keywords TCM， ferroptosis， and malignant tumors. We outlined the mechanisms of ferroptosis and its association with malignant tumors， and summarized the research progress on the prevention and treatment of malignant tumors through the modulation of ferroptosis by TCM monomers， single herbs， and compounds. The study aims to provide new perspectives for the prevention and treatment of malignant tumors by TCM.

Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

Malignant tumors are one of the major causes of death in the population. Owing to limited clinical treatments， susceptibility to drug resistance， and generally low cure rates of conventional therapies， new treatment strategies need to be explored. Compared with existing therapies， traditional Chinese medicine （TCM） has unique advantages， such as low side effects， in the treatment of malignant tumors. Ferroptosis is a recently characterized form of regulated cell death associated with iron metabolism imbalance， lipid peroxidation， antioxidant system malfunction and other aspects. Studies have shown that TCM regulates Fe³⁺， Fe²⁺， glutathione， glutathione peroxidase 4 and other substances related to ferroptosis， thereby affecting lipid peroxidation and antioxidant processes， and then inducing ferroptosis. Through these mechanisms， TCM plays a key role in inhibiting the growth and spread of tumor cells and is involved in multiple stages of malignant tumor progression. In this study， we systematically retrieved the literature indexed in PbuMed and China National Knowledge Infrastructure （CNKI） with the keywords TCM， ferroptosis， and malignant tumors. We outlined the mechanisms of ferroptosis and its association with malignant tumors， and summarized the research progress on the prevention and treatment of malignant tumors through the modulation of ferroptosis by TCM monomers， single herbs， and compounds. The study aims to provide new perspectives for the prevention and treatment of malignant tumors by TCM.

OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.