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.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Oxidative stress is an important pathophysiological pathway for the development and progression of ferroptosis. Under pathological conditions, the production of a large amount of reactive oxygen species （ROS） exceeds the buffering capacity of the antioxidant defense system, resulting in lipid peroxidation and cell ferroptosis in the state of oxidative stress. Cellular lipid peroxidation can generate toxic aldehydes, which interact with important biological macromolecules and break the normal function of cells. At present, it has been found that aldehyde dehydrogenase 2 （ALDH2） can eliminate these aldehydes and regulate the cycle of toxic aldehydes-ROS-oxidative stress-lipid peroxidation, thereby improving the prognosis of diseases associated with iron death. Ferroptosis and ALDH2 were introduced, and the current researches on ALDH2 were summarized to improve diseases associated with iron death, which can open up new directions for the subsequent research on the treatment of diseases associated with iron death.

ObjectiveTo explore the effects of "dryness pathogen" on a bronchial asthma rat model from the perspective of the prostaglandin D₂ （PGD₂）/eosinophil （EOS） axis. MethodsForty SD rats were randomly divided into five groups， blank group， asthma group， mild dryness asthma group， moderate dryness asthma group， and severe dryness asthma group， with 8 rats in each group. The asthma model was induced in the asthma group using ovalbumin （OVA）， while the asthma-dryness syndrome groups were modeled using a climate chamber combined with OVA to establish animal models of bronchial asthma with Northwest dryness syndrome. During modeling， general behavioral performance of the rats in each group was observed and recorded， and body weight， water intake， and asthma symptom scores were compared. On day 21 of the modeling， small animal respiratory system testing was used to measure respiratory rate and intermittent respiratory contraction index. Pathological changes in rat lung tissues were observed using HE staining. Giemsa staining was used to observe eosinophil （EOS） infiltration in lung tissues and calculate EOS counts. ELISA was used to detect serum levels of prostaglandin D₂ （PGD₂）， interleukin-5 （IL-5）， and interleukin-4 （IL-4）. Western Blot was used to detect eosinophil peroxidase （EPX） and prostaglandin D₂ receptor （CRTH2） protein levels in rat lung tissues. ResultsCompared to the blank group， the average water intake of rats in all asthma-dryness groups increased （P＜0.01）. The body weight of rats decreased in the moderate and severe asthma-dryness groups on day 14， and in all modelling groups on day 21 （P＜0.05 or P＜0.01）. Across all model groups， the asthma symptom score， respiratory rate， intermittent respiratory contraction index， EOS count in lung tissue， serum levels of PGD₂， IL-5， and IL-4， as well as the relative protein expression levels of EPX and CRTH2 in lung tissue all significantly increased （P＜0.01）. Compared to the asthma group， the water intake of rats in the mild， moderate， and severe asthma-dryness groups increased （P＜0.01）. On day 21 of the experiment， the body weight of rats in the moderate and severe asthma-dryness groups decreased （P＜0.05）， and the respiratory rate of rats in all asthma-dryness groups increased， as well as the serum levels of PGD₂， IL-5， and IL-4， and the relative protein expression levels of EPX and CRTH2 in lung tissues （P＜0.05 or P＜0.01）. Furthermore， in the moderate and severe asthma-dryness groups， the asthma symptom scores and intermittent respiratory contraction indices were elevated， and the EOS counts in lung tissue increased （P＜0.05 or P＜0.01）. Compared to the mild asthma-dryness group， serum levels of PGD₂， IL-5， and IL-4 in the severe asthma-dryness group increased， as well as the relative protein expression levels of EPX and CRTH2 in lung tissue （P＜0.05 or P＜0.01）. Pathological observation showed that rats in all asthma-dryness syndrome groups exhibited increased inflammatory infiltration in the lung tissue， alveolar wall thickening， luminal narrowing， pulmonary interstitial congestion， and aggravated viscous secretions. These pathological manifestations worsened as the degree of dryness increased. ConclusionThe "dryness pathogenic factor" can exacerbate bronchial asthma symptoms and lung tissue pathological damage through the PGD₂/EOS axis， and the damage progressively worsens with the increasing severity of the dryness pathogen.

Objective To investigate the diagnostic value of our regression model based on quantitative parameters of dual-energy CT and clinical features for stages T2 and T3 colorectal cancer.Methods A cross-section study was performed on 91 patients with colorectal cancer confirmed by postoperative pathology in our hospital from January 2022 to November 2023.All of them underwent dual-energy CT examination.According to the pathological T staging criteria of Chinese Colorectal Cancer Diagnosis and Treatment Standard(2020 Edition),they were divided into T2 group(n=43)and T3 group(n=48).Univariate analysis was used to compare the differences in quantitative CT parameters and clinical features between the 2 groups,and the obtained significant variables were employed to construct diagnosis models by univariate or multivariate logistic regression analysis.The area under receiver operating characteristic curve(AUC)of the CT parametric model and the model combined with clinical features was compared to evaluate the efficacy of diagnosing T2 and T3 stages.Results Univariate analysis showed that carcinoembryonic antigen(CEA),N stage,tumor location,tumor longest diameter(LD),CT value of virtual noncontrast(CT-VNC),fat fraction,electron density(Rho)and dual energy index(DEI)were significantly different between the T2 and T3 groups(P＜0.05).Multivariate logistic regression analysis found that N stage,tumor location,LD,fat fraction and DEI were independent risk factors for the diagnosis of stage T3.The AUC value of the model of above CT parameters in diagnosing stage T3 colorectal cancer was 0.671(95％CI:0.558～0.783),and the AUC value of the combined model of above CT parameters and clinical features was 0.886(95％CI:0.815～0.957),and statistical difference was observed in the AUC value between the combined model and the CT parametric model(P＜0.01).Conclusion The regression model constructed with dual-energy CT quantitative parameters combined with clinical features has high value in the preoperative diagnosis of stages T2 and T3 colorectal cancer before surgery.

Haloacetic acids(HAAs),as a class of disinfection byproducts in drinking water,pose potential threats to human health,so the rapid,accurate and simultaneous detection of HAAs is of great significance for ensuring drinking water safety.Aiming at the challenges in HAAs detection and risk analysis,a novel method for synchronous rapid detection of seven kinds of HAAs in drinking water based on in situ derivatization technology and headspace gas chromatography was developed in this study.Through single-factor optimization experiments,the optimal reaction parameters for in situ derivatization were determined,including the type and dosage of salting-out agent,the acidity of reaction system,the amount of phase transfer catalyst,the dosage of derivatization agent,and the extraction solvent volume.Methodologic validation showed that the seven kinds of HAAs exhibited excellent linear relationships within their respective detection concentration ranges(R2>0.998).The method detection limits(MDLs)ranged from 0.04 to 0.33 μg/L,and the limits of quantification(LOQs)were between 0.14 and 1.34 μg/L.For real water samples,the average spiked recoveries of the seven HAAs ranged from 90.9%to 107.7%,with relative standard deviation(RSDs)between 1.55%and 6.49%,and the HAAs contents in all tested samples were below the limits specified in the Standards for Drinking Water Quality(GB 5749-2022)of China.This method was featured with simple operation,fast analysis speed,high sensitivity,and good accuracy,providing an efficient and reliable technical support for routine monitoring of HAAs contaminants in drinking water and showing promising application value for widespread promotion.

AIM To study the chemical constituents from Tetrastigma hemsleyanum Diels et Gilg and their antitumor activity in vitro.METHODS Silica gel,ODS,Sephadex LH-20 and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activity in vitro was determined by MTT mothod.RESULTS Twenty-eight compounds were isolated and identified as triphyllin A(1),eruberin B(2),(2S,4R)-5,7-dihydroxy-4,4'-dimethyl-6,8-dimethyl-flavan-5-O-β-D-6-acetylglucopyranoside-7-O-β-D-glucopyranoside(3),eruberin A(4),abacopterin Ⅰ(5),matteucinol(6),homoerodictyol(7),(2S)-5,3',4'-trihydroxy-7-methoxy-flavanone(8),(2S)-5,2',5'-trihydroxy-7-methoxyflavanone(9),galinsonside B(10),quercetin-3-O-β-D-glucopyranoside(11),kaempferol 3-O-robinobioside(12),rutin(13),geniposide(14),jasminoside A(15),β-sitostenone(16),sitosterol palmitate(17),β-sitosterol(18),ursolic acid(19),hyptadienic acid(20),3,4-dihydroxybenzoic acid(21),3,4-dimethoxybenzoic acid(22),gallic acid(23),dibutylphthalate(24),bis-(2-ethylhexyl)phthalate(25),9-nonadecenoic acid(26),triacylglycerol(27),crocin Ⅰ(28).The IC50 values of compound 1 for human gastric adenocarcinoma cells BGC-823 and human colon cancer cells HCT-116 were(22.07±0.38),(20.67±0.11)μmol/L,respectively.The IC50 value of compound 9 for BGC-823 cells was(21.58±0.05)μmol/L,and the IC50 value of compound 4 for HCT-116 cells was(16.67±0.36)μmol/L.CONCLUSION Compounds 1-10,14-15 and 28 are first isolated from Tetrastigma genus.Compounds 1,4,9 have weak antitumor activity in vitro.

Objective Exploring the components of complex scenarios of healthcare surges triggered by major epidemics to provide a theorical basis for building resilience in healthcare organizations.Methods A hybrid analysis method is used to summarize macro-meso-micro multi-level and multi-source heterogeneous information,extract the elements of complex scenarios of medical surge and evaluate the rationality.Fault Tree Analysis method is used to clarify the logical relationship between various scenario elements and construct scenario reasoning paths.Results 10 scenario states,11 disaster-bearing,24 emergency management and 23 scenario results are summarized and extracted to form the key elements of complex surge scenarios.Among them,M4 expansion and coordinated scheduling of key positions,B2 conventional drug inventory emergency/insufficient core treatment drugs,B emergency medical material transportation breakage,S3 disease symptom spectrum shift to severe disease,R13 prevention and control awareness laxity,and M5 media information dissemination management are the key driving factors that promote a major turning point in the scenario.The most positive scenario result is the orderly operation of the medical service system,and the most negative scenario result is the paralysis of the medical service system.Conclusion Medical institutions need to improve emergency plans based on the complex evolution scenarios of medical surges and agile governance capabilities targeting key turning points,focus on dynamically expanding and scheduling personnel in key positions,strengthen material rotation and reserve mechanisms,maintain smooth emergency logistics channels,and improve efficient management of media and public opinion,so as to comprehensively improve overall resilience.

Objective:To investigate the characteristics of the endometrial microbiota in patients with varying degrees of intrauterine adhesion (IUA).Methods:This single-center cross-sectional observational study enrolled 115 patients with IUA who were treated at the Hysteroscopic Center of Fuxing Hospital, Capital Medical University, from May 2022 to October 2023. After quality control and data preprocessing, 81 samples met the inclusion criteria for analysis. Patients were grouped according to an established IUA scoring and grading system into mild IUA ( n=38) and moderate-to-severe IUA ( n=43). Endometrial tissue was collected under sterile conditions. Bacterial genomic DNA was extracted, the 16S rRNA V3-V4 region was amplified, and sequencing was performed on an Illumina platform. Differences in endometrial microbiota diversity and composition were compared between the two groups. Results:Patients with varying degrees of IUA exhibited comparable species richness, evenness and diversity of endometrial microbiota. At the phylum level, the endometrial microbiota across all subjects was predominantly composed of Proteobacteria, Firmicutes, Cyanobacteriota, Bacteroidota, and Actinobacteriota, with Proteobacteria (32.29%) and Firmicutes (23.82%) showing the highest mean relative abundances. At the genus level, Ralstonia (16.67%), Lactobacillus (13.45%), and Streptococcus (7.07%) were the most abundant genera. Group comparisons showed that the abundance of Ralstonia was higher in the mild IUA group, whereas Lactobacillus, Vibrio and Pseudoalteromonas were more abundant in the moderate-to-severe IUA group; however, these differences did not reach statistical significance (all P>0.05). LEfSe analysis further indicated that Lactobacillus, Vibrio, Pseudoalteromonas, Aeromonas, Ureaplasma and Acetobacterium were relatively enriched in the moderate-to-severe IUA group, while Geobacillus, Stomatobaculum and Fusicatenibacter were more abundant in the mild IUA group. Conclusion:The composition of the endometrial microbiota differs among patients with varying IUA severity. IUA progression may be associated with alterations in the endometrial microbiota; however, causal relationships and underlying mechanisms require further investigation.

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.