Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

OBJECTIVE To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis （AS）based on macrophage polarization. METHODS Using atorvastatin served as the positive control， the drug-containing serum of the Qingre huatan huoxue decoction was prepared to treat RAW264.7 macrophages. Macrophage viability， apoptosis rate， and the fluorescence intensities of CD86 and CD206 were measured， along with the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Apolipoprotei n E-deficient （ApoE －/－ ） mice （AS model mice） fed with a high-fat diet were randomly assigned to model group， atorvastatin group （2.6 mg/kg）， and low-， medium- and high-dose groups of Qingre huatan huoxue decoction （90， 180， 360 mg/kg）， respectively. C57BL/6J mice fed with a standard diet served as the normal control group， with 10 mice per group. The treatment group mice were administered the corresponding drugs intragastrically， once daily， for 8 consecutive weeks. Serum levels of TNF-α and IL-1β were measured in all groups. Lipid deposition in the aorta （assessed by the percentage of plaque in the entire aorta and aortic root） and morphological changes in the aortic root were observed. Expression levels of CD86 and CD206 in aortic tissue， as well as the protein expression levels of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， AMP-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， and peroxisome proliferator-activated receptor γ （PPAR-γ） in aortic tissues were all detected. RESULTS Cell experiment results showed that， at concentrations of 5-100 μg/mL， the drug-containing serum of the Qingre huatan huoxue decoction significantly increased RAW264.7 cell viability （ P ＜0.05）. The drug-containing serum of the Qingre huatan huoxue decoction at concentrations of 10， 50， and 100 μg/mL， along with atorvastatin， significantly reduced apoptosis rates， CD86 fluorescence intensity， and TNF-α and IL-1β levels in RAW264.7 cells， while markedly enhancing CD206 fluorescence intensity （ P ＜0.05）. Animal experiment results showed that， compared with the model group， all dosage groups of Qingre huatan huoxue decoction and the atorvastatin group showed significantly reduced/down-regulated levels of TNF-α and IL-1β in serum， along with decreased aortic total and root plaque percentages， CD86 expression， and iNOS protein expression. CD206 expression and Arg-1， p-AMPK/AMPK， PPAR-γ protein expression were significantly up-regulated （ P ＜0.05）. Pathological morphology of the aorta showed varying degrees of improvement. CONCLUSIONS The formula of Qingre huatan huoxue decoction exerts its anti-AS effects by regulating macrophage polarization， increasing the proportion of M2 macrophages， thereby effectively inhibiting AS plaque formation and reducing inflammatory responses.

With the continuous advancement of medical research, it is increasingly recognized that the human body functions as a highly coordinated complex system, and the development of diseases often involves intricate interactions among multiple subsystems, including organs, tissues, and cells. Conventional pharmacological research, which primarily focuses on isolated subsystems, tends to emphasize direct interactions between drugs and the molecular targets in diseased organs. However, this approach often falls short in addressing the multifaceted challenges posed by complex diseases such as metabolic disorders, autoimmune diseases, cancers, and aging. In recent years, inter-organ cross-talk and its role in diseases progression, as well as cross-organ effects of drug intervention, have gained significant attention. This has highlighted the potential for treating complex diseases through holistic regulation of multiple organs. Traditional Chinese medicine(TCM) has long embraced a holistic and systemic approach for treatment, with concepts such as the interdependence and mutual restraint of the five Zang organs, the interconnection of Zang organs and Fu organs, treating the Zang organ diseases by regulating the Fu organs, treating the child organ diseases to cure the parent organs, and treating upper organ diseases by regulating lower organs. These concepts provide valuable insights into exploring the pathways and molecular mechanisms underlying inter-organ cross-talk. Building on our previous work on indirect actions of TCM, this paper introduces the concept of indirect pharmacology mediated by intermediate substances, as a new extension of classical pharmacology. This approach aims to offer new perspectives and innovative ideas for understanding inter-organ cross-talk and discovering cross-organ therapeutic strategies.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

In recent years, it has become a new direction in the field of neuroscience to explore the mode characteristics, functional significance and interaction mechanism of resting spontaneous electroencephalography (EEG) and task-evoked EEG. This paper introduced the basic characteristics of spontaneous EEG and task-evoked EEG, and summarized the core role of spontaneous EEG in shaping the adaptability of the nervous system. It focused on how the spontaneous EEG interacted with the task-evoked EEG in the process of task processing, and emphasized that the spontaneous EEG could significantly affect the performance of tasks such as perception, cognition and movement by regulating neural activities and predicting external stimuli. These studies provide an important theoretical basis for in-depth understanding of the principle and mechanism of brain information processing in resting and task states, and point out the direction for further exploring the complex relationship between them in the future.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Rest/physiology* ; Cognition/physiology* ; Evoked Potentials/physiology* ; Task Performance and Analysis

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.