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 investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

OBJECTIVE To analyze the incidence of cyclosporine （CsA）-associated acute kidney injury （AKI） in hospitalized patients， identify influencing factors， and construct a risk prediction model. METHODS A single-center retrospective study was conducted， enrolling clinical data from hospitalized patients treated with CsA at the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital from January 2018 to July 2024. The patients were classified into AKI group and non-AKI group based on the occurrence of CsA-related AKI. Univariate analysis and multivariate Logistic regression analysis were used to identify independent risk factors for CsA-related AKI， and a risk prediction model was constructed and its performance was evaluated. RESULTS A total of 439 patients were included， of whom 54 developed CsA-related AKI， with an incidence rate of 12.30%. The occurrence of CsA-associated AKI was positively correlated with concurrent bacterial pulmonary infection， cytomegalovirus viremia， respiratory failure， renal insufficiency， gastrointestinal bleeding， and peripheral central venous catheterization （odds ratios of 763.750， 16.944， 41.933， 236.806， 17.537 and 212.789， respectively； P ＜0.05）； while uric acid， prealbumin， and calcium levels were negatively associated with it （odds ratios of 0.983， 0.967 and 0.058， respectively； P ＜0.05）. The prediction model constructed based on the above factors yielded a χ 2 value of 10.254 （ P ＞0.05） in the Hosmer-Lemeshow test. The average area under the curve （AUC） from 10-fold cross-validation was 0.885. The AUC of the receiver operating characteristic curve was 0.883， with a sensitivity of 84.3% and a specificity of 80.4%， respectively， at the optimal cutoff value of 0.1. CONCLUSIONS Six factors， including concurrent bacterial pulmonary infection and cytomegalovirus viremia， are positively associated with the occurrence of CsA-related AKI； while uric acid， prealbumin， and calcium levels are negatively associated. The Logistic regression model constructed based on these factors demonstrates good predictive performance and can assist clinic in conducting early risk assessment and personalized interventions.

Objective To explore the application value of fractional anisotropy(FA)analysis of RGB component transformation in different directions of fibers in substantia nigra in Parkinson's disease(PD).Methods There were 35 cases of PD and 37 cases of normal control group.After being performed by brain diffusion tensor imaging(DTI)scanning,the sequence was imported into 3DSlicense 5.6.0,and the diffusion module was used to implement pseudo color mapping based on FA,locate and segment substantia nigra,and use the substantia nigra mask as the tracking starting point.After forming tracing,fibers were imported into DTIANALYSIS 1.51,converting the RGB components into FA values for analysis,and visualized the analysis result.At the same time,fiber length,fiber density,and segmented FA point cloud percentage were compared.Results Compared with the normal group,the length of substantia nigra fibers in the PD group was shorter[(95.14±19.85)mm vs(115.99±21.39)mm,P＜0.01],and there was a statistical difference between the two groups.There was no statistical difference in fiber density[(0.07±0.05)/mm3 vs(0.10±0.12)/mm3,P＞0.05]between control group and PD group.The percentage of FA segment point clouds in the PD group was lower than that in the normal group at 0.9-1,but the principal component characteristics of the point cloud ratios in each FA segment were not significant.Conclusion Based on the transformation of RGB components into FA analysis,the length,density,and FA values of substantia nigra nerve fibers in PD patients can be quantified and visualized,providing a basis for the study of PD neural pathways.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.

Objective To compare the efficacy and safety of CT-guided percutaneous radiofrequency ablation(RFA)and cryoablation(CRYO)combined with synchronous biopsy of pulmonary nodules.Methods Totally 62 patients with pulmonary nodules who underwent CT-guided percutaneous ablation with either RFA(n=30)or argon-helium CRYO(n=32)combined with simultaneous biopsy were enrolled,and the regarding postoperative complication rates and 1-year local control outcomes were compared.Results All patients successfully completed both ablation and biopsy procedures.In RFA group,the mean diameter of lesion was(1.43±0.33)cm,and the biopsy positive rate was 90.00%(27/30).Post-biopsy intrapulmonary hemorrhage extent immediately increased by 0.60(0.28,1.63)cm.Hemoptysis,pneumothorax requiring chest tube placement and infectious cavities observed in 2(2/30,6.67%),6(6/30,20.00%)and 4 cases(4/30,13.33%),respectively,and the 1-year local control rate in RFA group was 90.00%(27/30).In CRYO group,the mean diameter of lesion was(1.59±0.34)cm,and the biopsy positive rate was 100%(32/32).Post-biopsy intrapulmonary hemorrhage extent increased by 1.20(0.60,1.83)cm.Hemoptysis occurred in 7 cases(7/32,21.88%),and pneumothorax requiring chest tube placement was noticed in 8 cases(8/32,25.00%),while no infectious cavity was observed.The 1-year local control rate in CRYO group reached 96.88%(31/32).Statistical difference of infectious cavity was found between groups(P＜0.05).Conclusion Simultaneous biopsy during CT-guided percutaneous RFA and CRYO for lung nodules were both efficient and safe,while the former with relative higher incidence of infectious cavity.

Objective:To investigate the immuno-inflammatory regulatory effects of the Qing Gan San Jie Xiao Ying Formula(QGSJXYF)on Hashimoto's thyroiditis(HT)by modulating thyroid cell-derived exosomes to provide experi-mental evidence for its immunomodulatory mechanisms.Methods:Nthy-ori-3-1 thyroid cells were treated with QGSJXYF-medicated serum,with untreated cells serving as controls.Exosomes from both groups were extracted and analyzed using nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and Western blot to assess concentration,size distribution,morphology,and the expression of characteristic exosomal markers.An inflammatory model of human T lymphocytes(H9)was established and co-incubated with normal exosomes(EXO-C group)or QGSJXYF-treated exosomes(EXO-T group).The levels of inflammatory cytokines in H9 cells were measured using Western blot(WB)and ELISA.Results:Exosome characterization showed that the particle concentration of Nthy-ori-3-1 cell-derived exosomes in both the control and QGSJXYF groups ranged from 1×109 to 1×1011/mL,with particle diameters between 80～300 nm.The exosomes exhibited a typical spherical or cup-shaped morphology with positive expression of TSG101,CD63,and HSP70.Compared with the inflammation model group and the EXO-C group,the EXO-T group significantly reduced the intracellular expression of IL-17A protein in H9 cells(P<0.05)and suppressed IL-17 and IL-6 levels in the cell supernatant(P<0.01).Conclusion:QGSJXYF may exert its anti-inflammatory and thyroid-protective effects by modulating the functional state of thyroid cell-derived exosomes,regulating the inflamma-tory microenvironment,and inhibiting the expression of inflammatory cytokines associated with Hashimoto's thyroiditis.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.