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.

Objective:The greater tuberosity angle(GTA)and critical shoulder angle(CSA)are commonly referred to as radiographic markers which were used to described morphology of the greater tu-berosity and acromion respectively.At present,most international studies focus on the correlation be-tween the above two parameters and rotator cuff tears(RCTs),and their diagnostic value and risk assess-ment.This study attempts to find out the trend of GTA and CSA changes and risk threshold of RCTs,as well as the protective factors and risk factors.Methods:In this study,130 individuals from May 2019 to December 2020 were recruited.According to Southern California Orthopedic Institute(SCOI)classifica-tion,the individuals were divided into four groups retrospectively:Group A,negative control group;Group B,partial tears(articular side);Group C,partial tears(bursal side);Group D,full-thickness tears.GTA and CSA were measured respectively on true anteroposterior position X-ray of shoulder with arm in neutral rotation and performed by the same trained technician team in single-blind.The correla-tions between RCTs and relevant factors were analyzed.Results:According to the area under the receiver operating characteristic curve(AUC),GTA and CSA of RCTs(Groups B,C and D)were 0.736 and 0.673 with 95％confidence interval(CI),the cut-off value of GTA and CSA of RCTs were 70.5° and 39.5° respectively.Comparing with the control group,RCTs groups had significant statistical differences in age and body mass index(BMI)(P＜0.05),especially the full-thickness RCTs(Group D),which was older than Groups A,B and C(P＜0.05,cut-off value:56.5 years old)and shorter than Groups A and B(P＜0.05,cut-off value:1.58 m).Analyzed from scatter plot and regression analysis,there was no linear correlation between GTA and CSA.There were no significant differences in gender,dominant shoulders and smoking between the RCTs groups and the control group(P＞0.05).Conclusion:Larger GTA(＞70.5°)and CSA(＞39.5°)would be highly predictive in diagnosing RCTs without linear cor-relation,and GTA has a higher diagnostic value in contrast.Subacromial impingement and shoulder de-generation occurred before RCTs.Patients with age＞56.5 years and height＜1.58 m were more likely to develop disease of full-thickness RCTs and no statistic differences in weight and BMI.Gender,domi-nant shoulder and smoking were neither risk factors nor protective factors.

Objective:To examine the validity and reliability of the Basic Psychological Needs Satisfaction and Frustration Scale(BPNSFS)in the adult population.Methods:A total of 488 adults were recruited and random-ly divided into 2 groups.One half(n=244)was utilized for item analysis and exploratory factor analysis,while the other half(n=244)was reserved for confirmatory factor analysis.One month later,a convenient sample of 100 in-dividuals was selected for retesting.The Depression-Anxiety-Stress Scale-21(DASS-21)and the Satisfaction with Life Scale(SWLS)were employed as criterion measures.Results:Both subscales of the BPNSFS demonstrated a 3-factor structure,explaining a total variance of 60.99％and 60.31％,respectively.The 3-factor model exhibited good fit indices(x2/df=1.85,2.47;RMSEA=0.06,0.08;CFI=0.95,0.94;TLI=0.94,0.92;SRMR=0.04,0.05).Scores on both subscales and their dimensions were significantly correlated with DASS-21 and SWLS scores(|r|=0.16-0.57,Ps＜0.001).The Cronbach α coefficients for the 2 subscales were 0.87 and 0.89,with Cronbach α values for each dimension ranging from 0.73 to 0.81.The test-retest reliabilities(ICC)for the 2 sub-scales were 0.84 and 0.80,with ICC values for each dimension ranging from 0.65 to 0.83.Conclusion:The validi-ty and reliability of the Chinese version of the Basic Psychological Needs Satisfaction and Frustration Scale demon-strate good measurement properties in assessing the adult population.

Objective This study established a qualitative and quantitative detection method for 9 new synthetic cannabinoids in e-cigarette oil using liquid chromatography-high resolution mass spectrometry.Methods E-cigarette oil was extracted with methanol,concentrated by nitrogen blowing under a water bath at 60℃,and separated using an Acquity UPLC? HSS T3(100 mm×2.1 mm,1.8 μm)column.Gradient elution was performed with ammonium acetate buffer solution(20 mmol/L)containing 0.1%formic acid and acetonitrile as the mobile phase.Detection was carried out in the positive ion mode of the HESI ion source using DDA(FullScan+dd-MS2)mode.Quantification was performed using the external standard method based on precise precursor ion peak areas,while qualitative analysis relied on retention times and characteristic fragment ions.Results The results showed that the standard curves of all 9 synthetic cannabinoids in blank e-cigarette oil matrix exhibited good linearity with R2 values>0.999.The limits of detection ranged from 0.0001 to 0.01 μg/g,and the limits of quantification ranged from 0.0003 to 0.03 μg/g.Recovery rates at low,medium,and high spiking levels in blank e-cigarette oil matrix ranged from 75.7%to 115%,with relative deviations<8.5%.Conclusion This method features a short instrument detection time of only 10 min,relatively simple operation,low detection limits,high accuracy,and good precision,making it applicable for rapid screening and quantitative analysis of synthetic cannabinoids in e-cigarette oil.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To analyze the spatiotemporal evolution patterns of mortality and disease burden of smoking-related prostate cancer(PCa)from 1990 to 2021 and to predict the future trends,so as to provide evidence-based insights for optimizing regional PCa prevention policies and smoking cessation interventions.Methods Based on data from the Global Burden of Disease Study(GBD)2021,annual mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs),and age-standardized rates(ASRs)for PCa across 204 countries and 21 regions from 1990 to 2021 were obtained.Estimated annual percentage change(EAPC)was used to assess the disease burden and mortality of smoking-related PCa across global,regional,socio-demographic index(SDI),and age groups.An autoregressive integrated moving average(ARIMA)model was employed to predict trends in these indicators up to 2050.Results In 2021,smoking-related PCa caused 12 992 global deaths,a 30.74％increase compared to 1990.However,from 1990 to 2021,the global age-standardized mortality rate(ASMR),age-standardized DALYs rate(ASDR),age-standardized YLDs rate(ASYR),and age-standardized YLLs rate(ASLR)for smoking-related PCa declined,with EAPCs being-1.43(95％CI:-1.77--1.12),-1.39(95％CI:-1.66--1.12),-0.41(95％CI:-0.67--0.15)and-1.51(95％CI:-1.78--1.23).In 2021,the region with the highest number of deaths from PCa was Asia(4663 deaths),followed by Europe(4647 deaths),and Oceania had the lowest number of deaths(9 deaths).From 1990 to 2021,the mortality rate of PCa in most regions generally showed a downward trend.High SDI regions showed the most significant declines in ASMR,ASDR,and ASLR[EAPCs:-3.17(95％CI:-3.31--3.02),-2.91(95％CI:-3.02--2.83),and-3.22(95％CI:-3.35--3.09)].For ASYR,only high-SDI regions exhibited a decline,whereas low-middle-SDI regions saw the largest increase[EAPC:1.26(95％CI:1.19-1.33)].In 2021,the number of PCa deaths was more concentrated in the age groups of 70-74 and 75-79,with 2312 and 2278 deaths,respectively.From 1990 to 2021,ASMR,ASDR,and ASLR showed an overall downward trend,EAPC were-2.84(95％CI:-3.21--1.83),-2.77(95％CI:-3.13--1.75),and-2.84(95％CI:-3.14--1.71),with the most significant decline observed in individuals aged 35-39.Projections to 2050 indicated continuing declines in all burden metrics,which would stabilize in later years.Conclusion Despite a global decline in smoking-related PCa burden over the past three decades,significant regional disparities persist,with low-and middle-income countries facing ongoing challenges.Implementing stricter tobacco control policies is critical to mitigating smoking-related health risks.

We analyzed the epidemiological features and spatial distribution characteristics of human brucellosis in Jining city from 2014 to 2023,to provide a reference for further development of targeted prevention and control strategies and measures.Descrip-tive epidemiological methods were used to analyze the epidemiological characteristics of brucellosis cases in Jining from 2014 to 2023.The spatial regional correlation of brucellosis incidence in Jining and the clustering patterns of local areas were studied through spatial autocorrelation analysis with townships as the basic unit.A total of 3 520 cases of brucellosis were reported in Jining from 2014 to 2023,and the average annual incidence rate was 4.23/100 000,thus indicating a fluctuating trend overall.Reported cases peaked from March to August,and a sex ratio of 2.71 males to 1 female was observed.The 40-59 year age group had the most reported cases(50.39％).The incidence of brucellosis in Jining showed an imbalanced spatial distribution.Brucellosis incidence showed a spatially clustered distribution(Moran's I>0,P<0.05).Hotspots were distributed primarily in Sishui,Qufu,and Zoucheng.A total of one class Ⅰ clustering area and one class Ⅱ clustering area were detected in the spatial and temporal scans,and were located in Sishui,Qufu,and Liangshan county.After pathogenic AMOS-PCR typing analysis,64 Brucella isolates collected from Jinan City from 2022 to 2024 were all of the sheep strain,and sheep biovar 3 was predominant(70.31％).In 2014-2023,although Jining City experienced a high incidence of brucellosis,a downward trend was observed.Brucellosis showed a spatial clustering pattern concentrated in the northeastern region.Therefore,awareness and education must be strengthened among brucellosis practitioners in cluster areas,to en-hance case surveillance,improve the level of protection,and achieve early detection and treatment.

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.