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.

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 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.

Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

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*