Kidney transplantation is the most effective treatment for end-stage renal failure, and antibody-mediated rejection remains the leading cause of late allograft loss. Macrophages, as central effectors of innate immunity, play a crucial role in the initiation, progression and tissue damage of antibody-mediated rejection. This article reviews the spatiotemporal dynamic evolution of macrophage polarization status in different stages of antibody-mediated rejection, the fine regulation of key signaling pathways for macrophage polarization, macrophage related molecules and the application prospects of targeted macrophage therapy. In depth analysis of the research progress of macrophages in antibody-mediated rejection, aiming to provide important theoretical basis for the development of precision diagnostic tools based on macrophages and novel immune intervention targets for antibody mediated rejection, ultimately promoting the improvement of long-term prognosis in kidney transplantation.

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.

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.

Zhusha Anshenwan is a classical traditional Chinese medicine （TCM） formula originating from LI Dongyuan's Treatise on the Differentiation of Endogenous and Exogenous Injuries （Nei Wai Shang Bian Huo Lun） of the Jin-Yuan period. It is composed of five medicinal ingredients： Cinnabaris （Zhusha）， Coptidis Rhizoma （Huanglian）， Angelicae Sinensis Radix （Danggui）， Rehmanniae Radix （Shengdihuang）， and Glycyrrhizae Radix et Rhizoma （Gancao）. Under the guidance of TCM theory， this formula is used to treat syndromes of disturbed spirit， including insomnia， palpitations， and anxiety， caused by hyperactivity of heart fire and deficiency of Yin-blood， and it also exerts auxiliary anticonvulsant effects in epilepsy and related conditions. However， the potential neurotoxicity， hepatotoxicity， and nephrotoxicity of its monarch drug， Cinnabaris （mainly composed of mercuric sulfide， HgS）， together with the risk of in vivo accumulation， have rendered its clinical application controversial， and it has not yet been formally included in the Pharmacopoeia of the People's Republic of China. In addition， restrictions imposed by the Minamata Convention on Mercury have led to an increasing shortage of natural medicinal Cinnabaris resources， making the evaluation of the efficacy and safety of synthetic Cinnabaris particularly urgent. This contradiction highlights the complexity of safety evaluation for traditional medicines. Existing studies indicate that Zhusha Anshenwan exhibits definite pharmacological activities in calming the mind， improving sleep， and regulating emotional disorders. Moreover， other components of the formula may exert antagonistic effects on the toxicity of Cinnabaris， and reports of severe mercury poisoning caused by standardized clinical use of this prescription are extremely rare. Research suggests that other ingredients in the compound formula， such as Rehmanniae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma， may effectively alleviate the hepatorenal toxicity of Cinnabaris through mechanisms including modulation of the gut microbiota， formation of mercury complexes， and direct protection of target organs. This article aims to systematically review the progress in pharmacodynamic research on Zhusha Anshenwan， to explore its mechanisms of action in depth， and to analyze the toxicokinetic characteristics and safety risks of Cinnabaris， as well as the scientific connotations of toxicity reduction and efficacy enhancement achieved through compound compatibility. In addition， it compares Zhusha Anshenwan with other commonly used sedative formulas， with the aim of providing a scientific basis and forward-looking perspectives for the safe and rational application and in-depth development of this classical prescription in a modern context， and of emphasizing the important value of holistic research on TCM compound formulas in addressing the challenges of single-component toxicity.

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.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets