Objective: To investigate the current knowledge status of transfusion medicine among pediatricians/postgraduates and the reliability of large language models (LLMs) for assisted learning, and to assess changes in pediatricians' transfusion medicine knowledge before and after the implementation of the "Pediatric Transfusion Guideline" (hereafter referred to as the "Guideline"). Methods: In January 2022 (prior to the implementation of the "Guideline"), a questionnaire was developed based on the "Guideline" content and distributed to pediatricians. Subsequently, in July 2025 (after the implementation of the "Guideline"), the "Pediatric Transfusion Medicine Knowledge Questionnaire" was designed based on the content of the January 2022 questionnaire. This questionnaire survey was conducted on pediatricians/postgraduates and LLMs. We analyzed the level of transfusion medicine knowledge among pediatricians/postgraduates and the reliability of LLMs for assisted learning, and compared the accuracy of pediatricians' responses before and after "Guideline" implementation. Results: The survey results after the implementation of the "Guidelines" revealed that pediatricians/postgraduates achieved response accuracy rates exceeding 80% on the topic of "Patient Blood Management". However, response accuracy rates were below 30% for topics including "Types and Indications of Blood Components/Products" and "E-valuation of Transfusion Efficacy". The pediatricians' accuracy rates for related questions before and after the implementation of the "Guidelines" were 14.7%-68.9% and 3%-38%, respectively, and the comparison of accuracy rates for each question showed significant differences (P<0.001). The accuracy rates of the LLMs on the questionnaire were all below 90%. Among them, Doubao (81.1%) and Kimi (86.4%) achieved relatively higher accuracy rates, while Tencent Yuanbao (Hunyuan) had the lowest accuracy rate at only 59.5%. Conclusion: The implementation of the "Guideline" may have improved pediatricians' knowledge level of pediatric transfusion medicine. However, their knowledge level of pediatric transfusion remains low, and LLMs cannot yet provide absolutely reliable guidance. Systematic training in pediatric transfusion medicine is urgently needed.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

This paper systematically expounds the core challenges and development vision facing transfusion medicine and discipline construction in China under the strategic goals of achieving "Chinese modernization" and "Healthy China". This article puts forward for the first time the "blood transfusion view" of Chinese blood transfusion practitioners and elaborates on key challenges in the field, including the disciplinary system, talent pool, service balance, technical bottlenecks and standardization in emerging fields. To address the challenges, it is urgently necessary to establish the disciplinary status of transfusion medicine, improve talent cultivation, enhance the integration of scientific research and technology, optimize transfusion assessment, promote autologous blood transfusion, advance the localization of evidence-based medicine, and expand the management functions of biological therapy. The ultimate goal is to build a modern blood transfusion system led by science and technology and with Chinese characteristics to safeguard people's health.

Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Objective:To investigate the current status of breast reconstruction after breast cancer surgery in hospitals in China.Methods:This study was a cross-sectional study using convenience sampling. A self-designed survey questionnaire was used to investigate nurses of department of breast diseases in China from May to August 2023. The content of the questionnaire included four aspects: identification information, basic hospital information, the implementation situation of breast reconstruction after breast cancer surgery, and the situation of medical and nursing human resources for breast reconstruction, with a total of 39 items. Statistical analysis was performed using SPSS 26.0 software. The non-normally distributed measurement data were expressed as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Numeric data were expressed as frequency and percentage, and comparisons between groups were made using the χ2-test or Fisher’s exact probability method. P<0.05 indicated that the difference was statistically significant. Results:A total of 212 public hospitals from 31 provinces, autonomous regions and municipalities participated in the survey. Two hundred and three hospitals (95.8%) returned valid data, including 155 Grade Ⅲ Level A hospitals, 19 Grade Ⅲ Level B and C hospitals, and 29 Grade Ⅱ hospitals. There were 157 general hospitals, 32 specialized cancer hospitals, and 14 other hospitals. Thirty-nine hospitals did not perform breast reconstruction surgery. A total of 164 hospitals (80.8%) had already carried out breast reconstruction surgery, among which the proportion of breast reconstruction in Grade Ⅲ Level A hospitals [90.3% (140/155)] was significantly higher than that in Grade Ⅲ Level B and C hospitals [52.6% (10/19)] and Grade Ⅱ hospitals [48.3% (14/29)] ( P<0.01). The proportion of breast reconstruction in specialized cancer hospitals [96.9% (31/32)] was significantly higher than that in general hospitals [79.0% (124/157)] and other types of hospitals [64.3% (9/14)] ( P<0.05). Among the 164 hospitals, 310 (150, 637.5) patients underwent breast cancer surgery and 30 (10, 100) patients underwent breast reconstruction in 2022. The proportion of patients undergoing breast reconstruction surgery among breast cancer surgery patients was 13.3% (4.0%, 20.0%). The number of patients receiving immediate breast reconstruction was 11 (2.5, 46.5) cases, and the number of those receiving delayed breast reconstruction was 5 (0, 18.5) cases. Among 203 hospitals, the median proportions of breast oncoplastic surgeons and specialized nurses among healthcare providers in breast surgery departments were 28.6% (2/7) and 75.0% (12/16), respectively. In comparison of the 164 hospitals offering breast reconstruction surgery and 39 hospitals not, the median numbers of breast oncoplastic surgeons were 3 (1, 8) versus 1 (0, 3), and qualified breast reconstruction nurses were 12 (6, 16) versus 1 (0, 8), respectively. All differences were statistically significant (all P<0.01). Conclusion:About 80% of hospitals in China have offered breast reconstruction procedures after breast cancer surgery, and the proportion of Grade Ⅲ Level A hospitals and specialized cancer hospitals is higher than that of other types of hospitals. The proportion of patients undergoing breast reconstruction after breast cancer surgery is relatively low, and there is a considerable potential of improvements. Breast oncoplastic surgeons and nurses are insufficient, so it is necessary to strengthen the training of specialized medical staff and improve surgical techniques and the level of nursing services simultaneously, so as to improve the quality of life of breast cancer patients.