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.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

ObjectiveTo evaluate the clinical efficacy and safety of the Qishen Liuwei presoription for senile hypertension complicated with frailty （of Qi deficiency and blood stasis pattern， or deficiency of both spleen and kidney pattern）. MethodsA single-center， randomized controlled clinical trial design was employed in this study. Sixty-four eligible patients， treated at the Cardiology Outpatient Clinic of Dongfang Hospital， Beijing University of Chinese Medicine between June 2024 and February 2025， were randomly allocated into an observation group or a control group， with 32 patients in each group. Both groups received standard conventional antihypertensive therapy， while the observation group additionally received the Qishen Liuwei Formula （one dose per day， in separate servings in the morning and evening）. For both groups， a treatment course consisted of 4 weeks， followed by a 2-month follow-up period. Then， the primary indicator （Fried frailty phenotype scores）， along with secondary indicators including traditional Chinese medicine （TCM） syndrome scores and changes in blood pressure were observed before and after treatment. ResultsRegarding Fried frailty phenotype scores， the observation group exhibited significantly improved grip strength， 4.57 m walk time， the duration of weekly walks， ''effort required for any activity''， and ''inability to walk forward'' after treatment， while only the latter two indicators were significantly improved in the control group （P<0.05）. Compared with the control group， the observation group demonstrated significantly superior improvement in the duration of weekly walks， ''effort required for any activity''， and frailty （P<0.05）. For total TCM syndrome scores， both groups displayed significantly decreased total TCM syndrome scores （P<0.05） after treatment， and the decrease was more significant in the observation group （P<0.05）. Regarding office blood pressure， both groups showed significantly decreased diastolic blood pressure and mean arterial pressure after treatment， while the observation group also showed significantly decreased systolic blood pressure （P<0.05）. During treatment， one case of facial rash occurred in the observation group， representing an adverse reaction rate of 3.13% （1/32）. The rash resolved one week after discontinuation of medication. No adverse reactions occurred in the control group during treatment. No statistically significant difference was observed in the incidence of adverse reactions between the two groups. ConclusionFor senile hypertension complicated with frailty， the Qishen Liuwei presoription effectively improves physical activity， muscle strength， frailty-related symptoms， and TCM syndrome remission. When combined with Western medicine， the Formula contributes to stable blood pressure control and demonstrates a favorable clinical safety profile， indicating its clinical application potential.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists' understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

A serum metabolomics analysis method based on gas chromatography-mass spectrometry(GC-MS) was used to investigate the metabolic regulation mechanism of Hericium erinaceus(H. erinaceus) polysaccharides on radiation injury. A mouse model of radiation injury was established by ~(60)Co-γ irradiation. High and low dose groups of H. erinaceus polysaccharide injection were designed, and Rubiae Radix et Rhizoma extract was set as the positive control group to investigate the therapeutic effects and metabolic reaction pathways of H. erinaceus polysaccharides on radiation injury. The metabolites of serum samples were collected by GC-MS, and principal component analysis(PCA) was conducted to establish the metabolic profiles of each group of mice. Partial least squares discriminant analysis(PLS-DA), t-test(P<0.05), and variable importance in the projection(VIP>1) were used to screen out the differential metabolite. Metabolite identification and construction of related metabolic pathways and metabolic networks were achieved by using online databases such as HMDB and METLIN. The results showed that 12 differential metabolites in the serum of mice irradiated at 6.5 Gy that were associated with the radiation injury model, including lactic acid, alanine, urea, serine, threonine, glycerol, L-5-oxoproline, L-lysine, stearic acid, stearic acid, oleic acid, and 1-monopalmitoylglucoside. Two metabolic pathways were enriched: glycerolipid metabolism and metabolism of glycine, serine, and threonine. 18 differential metabolites in the serum of mice irradiated at 8.5 Gy were associated with the radiation injury model, including lactic acid, alanine, urea, L-leucine, glycerol, nonanoic acid, serine, threonine, L-5-oxoproline, phenylalanine, L-ornithine, 1,5-dehydroorbital, L-lysine, L-tyrosine, pectic, oleic, stearic, and cholesterol. Four metabolic pathways were enriched: phenylalanine, tyrosine, and tryptophan synthesis, phenylalanine metabolism, glyceride metabolism, and glycine, serine, and threonine metabolism. It was suggested that H. erinaceus polysaccharides could intervene in radiation injury by altering amino acid and fatty acid synthesis in mice. It was assumed that H. erinaceus polysaccharides regulated the level of metabolic pathways through lipid metabolism and amino acid metabolism, thus affecting energy metabolism and amino acid metabolism and exerting its therapeutic effect on radiation damage.
Animals ; Mice ; Metabolomics/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Polysaccharides/pharmacology* ; Male ; Hericium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Metabolome/drug effects* ; Gamma Rays/adverse effects*

To clarify the occurrence and distribution of broad bean wilt virus 2(BBWV2) on Rehmannia glutinosa, this study collected 87 R. glutinosa samples with typical symptoms of viral disease such as chlorosis and crumple from Wenxian county and Wuzhi county in Jiaozuo city, Henan province and Qiaocheng district in Bozhou city, Anhui province. The BBWV2 CP target band was amplified from 37 R. glutinosa samples by RT-PCR technology. The total detection rate reached 42.5%, among which 43.0% was detected in samples from Henan province. The detection rate in samples from Anhui province was 37.5%. 37 BBWV2 CP sequences were obtained by cloning and sequencing of BBWV2 positive samples(data has been submitted to GenBank, accession numbers: PP407959-PP407995), and the sequence analysis of these CP sequences with 91 other BBWV2 isolates in GenBank showed a high genetic diversity with a consistency rate of 70.8%-100%. Meanwhile, phylogenetic analysis showed that BBWV2 could be divided into three groups according to CP sequences, among which the BBWV2 in R. glutinosa isolates obtained in this study were all located in group 3. This study identified the differences in the occurrence, distribution, and genetic diversity of BBWV2 in R. glutinosa from Henan province and Anhui province and provided a theoretical basis for the prevention and control of BBWV2.
Rehmannia/virology* ; Phylogeny ; Plant Diseases/virology* ; China ; Molecular Sequence Data ; Fabavirus/classification*

Acute myocardial infarction and acute upper gastrointestinal bleeding are both critical internal medicine conditions. The incidence of acute upper gastrointestinal bleeding in patients with acute myocardial infarction ranges from 5.31% to 8.90%, with a mortality rate as high as 20.50% to 35.70%. The pathogenesis may be related to the use of antiplatelet and anticoagulant drugs, as well as stress-induced injury. In treatment, the contradiction between antiplatelet/anticoagulation therapy and bleeding has made this disease a significant challenge in modern medicine. Therefore, re-exploring the etiology, pathogenesis, treatment principles, and methods of traditional Chinese medicine(TCM) for acute myocardial infarction and acute upper gastrointestinal bleeding is of great clinical importance. The research team has been working year-round in the coronary care unit(CCU), managing a large number of such severe patients. By revisiting classic texts and delving into the foundational theories of TCM and historical medical literature, it has been found that this disease falls under the category of "distant blood" in the Synopsis of the Golden Chamber. In terms of etiology, it is primarily associated with weakness of healthy Qi and damage caused by drug toxicity. In terms of pathogenesis, in the acute stage, it mainly manifests as insufficient spleen Yang, deficiency of spleen Qi, and failure of the spleen to control blood. In the remission stage, it is characterized by deficiency of both heart Qi and spleen blood. For treatment, during the acute stage, Huangtu Decoction is used to warm Yang and restrain blood, while in the remission stage, Guipi Decoction is administered to tonify Qi and nourish blood. During the treatment process, for patients with acute myocardial infarction complicated with acute upper gastrointestinal bleeding, it is crucial to flexibly apply the treatment principles of "Nil per os" in western medicine and "where there is stomach Qi, there is life; where there is no stomach Qi, there is death" in TCM. Early intervention with Huangtu Decoction can also prevent bleeding, with large doses being key to achieving hemostasis. It is important to address the pathogenesis of heat syndrome in addition to the core pathogenesis of Yang deficiency bleeding and to emphasize the follow-up treatment with Guipi Decoction for a successful outcome.
Humans ; Gastrointestinal Hemorrhage/etiology* ; Myocardial Infarction/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Acute Disease