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.

OBJECTIVE To evaluate the cost-effectiveness of zolbetuximab combined with chemotherapy as first-line treatment for CLDN18.2-positive and HER2-negative advanced gastric cancer from the perspective of China’s healthcare system. METHODS Based on individual data from the GLOW clinical trial involving CLDN18.2-positive and HER2-negative patients with advanced gastric cancer， a comparison was made between the zolbetuximab combined with chemotherapy regimen and the chemotherapy alone regimen. A dynamic Markov model was employed for simulation， with a cycle length of 21 days and a time horizon of ten years. A cost-utility analysis was employed， with both costs and health outcomes discounted at an annual rate of 5%. The primary outcome measures included total cost， quality-adjusted life years （QALY） and incremental cost-effectiveness ratio （ICER）， with the willingness-to-pay （WTP） threshold set at three times China’s per capita gross domestic product in 2024 （287 247 yuan/QALY）. One-way analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Furthermore， scenario analysis and threshold analysis were conducted to explore the impact of drug price adjustments on cost-effectiveness and the threshold price. RESULTS Compared with the chemotherapy alone regimen， the ICER of zolbetuximab combined with chemotherapy was 2 611 943.00 yuan/QALY. One-way sensitivity analysis indicated that the utility value of the progression free survival， the cost of zolbetuximab and body surface area were the three most influential parameters affecting the ICER. The results of the probabilistic sensitivity analysis showed that when the WTP threshold was set at 2 617 450 yuan/QALY， the probability that the combined regimen was cost-effective approached 50%. Scenario analysis revealed that only when the price of zolbetuximab was reduced to 10% of the baseline price did the ICER of the combined regimen fall below the aforementioned WTP threshold. Threshold analysis further indicated that when the unit price of zolbetuximab dropped to 3.81 yuan/mg， the probability of the combination regimen being cost-effective was approximately 50%. CONCLUSIONS From the perspective of China’s healthcare system， zolbetuximab combined with chemotherapy regimen as first-line treatment for CLDN18.2-positive and HER2-negative advanced gastric cancer is not cost-effective compared with chemotherapy alone regimen. When the unit price of zolbetuximab drops to 3.81 yuan/mg or below， the regimen becomes cost-effective.

ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）. Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg^-1）， and betahistine group （1.62 mg·kg^-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43. ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）. ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） as first-line therapy for advanced gastric cancer. METHODS PubMed， Web of Science， Embase， The Cochrane Library， Wanfang Data， CNKI， and VIP databases were searched to collect phase Ⅲ clinical randomized controlled trials （RCTs） on ICIs as first-line therapy for advanced gastric cancer， as well as abstracts from relevant oncology academic conferences. The search period spanned from database inception to June 1， 2025. After screening literature， extracting data， and assessing quality， a network meta-analysis was performed using R software version 4.3.2. RESULTS A total of 8 studies involving 7 801 patients were included. Network meta-analysis results showed that， in terms of efficacy， compared with chemotherapy （Chemo）， SHR-1701_Chemo， Cadonilimab_Chemo， Sintilimab_Chemo， Pembrolizumab_Chemo， and Tislelizumab_Chemo significantly prolonged median overall survival （OS） and median progression free survival （PFS） in patients （P＜0.05）； whereas Nivolumab_Chemo only significantly improved median PFS （P＜0.05）. Surface under the cumulative ranking curve （SUCRA） results indicated that the top 2 interventions for median OS were SHR-1701_Chemo and Cadonilimab_Chemo； for PFS， the top 2 were Cadonilimab_Chemo and SHR-1701_Chemo. For patients with combined positive score （CPS） ≥5 points for programmed death-ligand 1 （PD-L1）， Cadonilimab_Chemo and SHR- 1701_Chemo also demonstrated the optimal OS and PFS benefits （P＜0.05）. Regarding safety， there were no statistically significant differences among the interventions in the incidence of any adverse events （AEs） or grade ≥3 AEs （P＞0.05）. The SUCRA ranking for the incidence of any AEs showed the top 2 were SHR-1701_Chemo and Chemo； for grade ≥3 AEs， the top 2 were Chemo and Sugemalimab_Chemo. CONCLUSIONS For patients with advanced gastric cancer， Cadonilimab_Chemo and SHR-1701_Chemo demonstrate the best benefits in terms of OS and PFS， with their advantages remaining clear in patients with PD-L1 CPS≥5 points. In terms of safety， the risk of developing any AEs and grade ≥3 AEs is relatively lowest with Chemo.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Objective: To investigate the precise detection methods for weak partial D type 15 and evaluate their implications for blood transfusion safety, along with the development of corresponding strategies. Methods: A combination of serological methods, including the microplate method, indirect antiglobulin tube method, and microcolumn gel card method, was employed to identify RhD-negative and RhD variant samples. RhD-negative samples were screened for the presence of RHD genes using whole-blood direct PCR amplification. Subsequently, RhD variant samples and RhD-negative samples containing RHD genes underwent full-coding-region sequencing of the RHD gene to confirm their genotypes. The genotyping results were further correlated with the serological test findings for comprehensive analysis. Results: Among 615 549 first-time healthy blood donors, 3 401 samples with an RhD-negative phenotype and 156 samples with RhD variant were identified. Of the 3 401 RhD-negative samples, 1 054 were found to harbor RHD genes. Gene sequencing analysis of the 156 RhD variants and the 1 054 serological negative samples revealed that 89 samples contained the RHD 15 (c. 845G>A) allele. Conclusion: The integration of serological testing methods and genotyping technologies for the precise determination of RhD blood type plays a critical role in ensuring the safety and compatibility of blood transfusions.

[摘 要] 目的：探讨肌营养不良蛋白-ɑ（DTNA）在胃癌组织中的表达特征、生物学功能及相关的调控机制。方法：基于公共数据库采用生物信息学方法分析预测DTNA基因在胃癌中的表达情况及与胃癌预后相关性。采用qPCR技术及免疫组化技术检测胃癌组织及细胞中DTNA的表达情况；采用卡方检验分析DTNA与胃癌临床病理特征之间的相关性，Kaplan-Meier生存分析法评估DTNA的表达水平与患者预后的关系。采用CCK-8、Transwell实验检测DTNA基因对胃癌MGC-803细胞增殖、迁移及侵袭的影响；RNA干扰、qPCR及WB实验检测远上游元件结合蛋白1（FUBP1）对MGC-803细胞中DTNA表达的影响。结果：生物信息学分析发现，DTNA在胃癌组织中表达高于癌旁组织且其高表达与胃癌的不良预后相关。DTNA在胃癌组织（P < 0.000 1）和细胞（P < 0.05）中表达上调，与T分期（P < 0.001）及TNM分期（P = 0.001）有正向关联，且与不良预后有正向关联（Log-Rank P = 0.0039）。敲减DTNA可以显著抑制MGC-803细胞的增殖、迁移和侵袭能力（均P < 0.01）；FUBP1下调可降低DTNA的表达（P < 0.01）。结论：DTNA在胃癌组织及细胞中表达上调且与病情进展及不良预后相关；敲减DTNA能抑制胃癌MGC-803细胞的增殖、迁移和侵袭，其表达受FUBP1调控。

OBJECTIVE To evaluate the efficacy and safety of first-line treatments regimens for human epidermal growth factor receptor 2 （HER2）-positive advanced gastric cancer. METHODS Computer searches were conducted on databases such as Web of Science， Embase， CNKI， and VIP in both Chinese and English， and abstracts of papers from the annual meetings of the European Society of Oncology and the American Society of Clinical Oncology were screened. Collected randomized controlled trials （RCTs） on first-line treatment for HER2-positive advanced unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients， with a retrieval period from database establishment until April 1， 2025. A network meta-analysis was conducted by two researchers who independently screened literature， extracted data， and evaluated the risk of bias in the study. RESULTS A total of 5 RCTs involving 2 797 patients and encompassing 6 treatment regimens were ultimately included. In the assessment of overall survival， there was a trend towards survival benefit for trastuzumab combined with chemotherapy （Tra_chemo）， pertuzumab combined with trastuzumab and chemotherapy （Per_Tra_chemo）， high-dose trastuzumab combined with chemotherapy （TraHD_chemo）， lapatinib combined with chemotherapy （Lap_chemo）， and pembrolizumab combined with trastuzumab and chemotherapy （Pem_Tra_chemo） compared to chemotherapy alone （chemo）； however， the differences were not statistically significant （P＞0.05）； the top two treatment regimens in terms of the surface under the cumulative ranking curve （SUCRA） were Pem_Tra_chemo （77.8%） and TraHD_chemo （74.2%）. For progression-free survival， there was statistical significance between Per_Tra_chemo and chemo， Pem_Tra_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Per_Tra_chemo （83.0%） and Pem_Tra_chemo （82.8%）. Regarding objective response rate， there was statistical significance between Pem_Tra_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Pem_Tra_chemo（87.4%）and Per_Tra_chemo（72.2%）. In terms of safety， there was statistical significance in the incidence of any level of adverse events between Lap_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were chemo（87.1%）and Pem_Tra_chemo（53.8%）. Lap_chemo exhibited a higher incidence of grade ≥3 adverse events compared to chemo， and Per_Tra_chemo showed a higher incidence compared to Tra_chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Tra_chemo （79.0%） and chemo （77.6%）. CONCLUSIONS In the first-line treatment of HER2-positive advanced gastric cancer， Pem_Tra_chemo and Per_Tra_chemo regimens have relatively good efficacy， but the safety risks are relatively high， requiring close attention and whole- process management.

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*