ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.

Objective To investigate the drivers,stakeholders,core tasks,and differentiated development models of digital transformation in Chinese hospitals,develop a hospital digital transformation model,and propose advancement pathways.Methods Leveraging ROCCIPI theory,socio-technical systems theory,and social network theory,a multiple case study approach was employed to analyze four representative Chinese hospitals,examining the driving factors,social network relationship,and core tasks of digital transformation.Results Hospital digital transformation is a complex process driven by regulations,opportunities,and capabilities,requiring efficient collaboration among stakeholders focused on patient services,clinical operations,hospital management,and security.It identified three development models-ecology-oriented,regional integration,and grassroots enhancement—based on the distinct characteristics of the hospitals.A theoretical model for digital transformation in four Chinese hospitals was developed,along with proposed pathways and strategies.Conclusion It presents a digital transformation model and advancement pathways for hospitals through multiple case analyses,addressing the limited perspectives of existing research and providing a reference for practice.

Pinellia ternata， belonging to the Pinellia genus within the Araceae family， is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation， necessitating urgent new variety protection efforts. The distinctness， uniformity， and stability （DUS） testing of the plant variety is the basis for protecting new plant varieties， and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata， agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years， and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits， 19 leaf traits， six flower traits， two fruit traits， two tuber traits， five bulbil traits， and one ploidy trait. These traits could be divided into 22 quality characters， 12 quantitative characters， and four pseudo-quantitative characters， as well as seven groups， including plants， leaves， flowers， fruit， tubers， bulbils， and ploidy. By searching for standard traits， 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties， safeguarding breeders' rights， and promoting the development of the P. ternata industry.

Objective To analyze the drug resistance and genomic characteristics of clinically isolated hypermuco-viscous Klebsiella pneumoniae(hmKp).Methods Klebsiella pneumoniae isolated from clinical specimens from the sentinel hospitals of National Pathogen Identification Network in Huai'an City from 2019 to 2023 were collected,strains were identified by VITEK 2 Compact,mucus phenotype was determined by string test,resistance of hmKp was determined by microbroth dilution method.Molecular typing was conducted by whole-genome sequencing tech-nology,annotation of virulence and resistance genes carried by strains was performed.Results A total of 60 strains of hmKp were collected,mainly isolated from sputum specimens(33.33％)and blood specimens(28.33％).The average genome size of 60 strains was 5.6 Mb,with an average GC content of 57.09％.Multilocus sequence typing(MLST)showed that there were 28 ST types,with the dominant ST types being ST1 1(11.67％),ST15(11.67％),and ST412(10.00％).Core genome MLST(cgMLST)analysis revealed that some strains were highly homologous,and no outbreak strains were found.Multidrug-resistant strains accounted for 60.00％,while imipe-nem-resistant strains accounted for 28.33％.64 types of resistance genes were carried,84.38％of which were loca-ted on mobile element.The carriage rates of fosfomycin-related resistance genes and extended-spectrum β-lactam an-tibiotic-related resistance genes were relatively high in the strains,at 100％and 98.33％,respectively.Among car-bapenem-resistance gene blaKPC-2,21.67％was carried by ST11,ST1,and ST15 strains,among bla NDM-5 gene,3.33％was carried by ST76 strain.A total of 101 virulence genes were carried,most were Colibactin and type Ⅵsecretion system-related virulence genes.All strains carried capsule synthesis regulation-related genes(rcsA,rcsB),efflux pump-related genes(acrA,acrB),and enterobacterin-related genes(entABCEF,fepABCDFG,fes).Conclusion Clinically isolated hmKp in Huai'an exhibits multidrug resistance,with dominant ST types ST11,ST15,and ST412,carrying multiple horizontally transferable resistance and virulence genes,prevention and control measures should be strengthened.

BACKGROUND:β-Defensin has the ability against influenza A virus and inhibits a series of inflammatory responses induced by influenza A virus infection within cells.There have been no reports on whether hemagglutinin 1 from influenza A virus can induce the secretion of mouse β-defensin and interferon-γ when acting in mouse tracheal epithelial cells.OBJECTIVE:To investigate the effect of recombinant hemagglutinin 1 on the production levels of mouse β-defensin and interferon-γ in mouse tracheal epithelial cells.METHODS:Primary mouse tracheal epithelial cell were divided into six groups:blank control group(Control),recombinant hemagglutinin 1 group(200 ng/mL),recombinant hemagglutinin 1+influenza A virus group,influenza A virus group(2×TCID50),recombinant hemagglutinin 1+inactivated influenza A virus group,and inactivated influenza A virus(I)group.After the mouse tracheal epithelial cells in each group were treated for 4,8,or 24 hours,hematoxylin-eosin staining was used for pathological observation.The mRNA levels of mouse β-defensin 2,3,and 4,and interferon-γ were detected by qRT-PCR.The protein levels of mouse β-defensin 2,3,and 4 were measured by enzyme-linked immunosorbent assay,and the protein expression of interferon-γ was detected by western blot.RESULTS AND CONCLUSION:(1)The recombinant hemagglutinin 1 acting alone or in combination with influenza A virus could cause different pathological changes in tracheal epithelial cells.Phenomena such as vacuolation,nuclear pyknosis and cell fusion could be observed in the cells.(2)Compared with the control group,recombinant hemagglutinin 1 alone or in combination with influenza A virus or inactivated influenza A virus significantly induced the production of mouse β-defensin 2,3,and 4(P<0.05)and interferon-γ in mouse tracheal epithelial cells(P<0.05).These results indicate that recombinant hemagglutinin 1 alone or in combination with influenza A virus can induce the production of mouse β-defensin 2,3,and 4 and interferon-γ in mouse tracheal epithelial cells.

Non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths worldwide, remains a significant clinical challenge despite advances in immune checkpoint inhibitors therapy, with drug resistance persisting as a major obstacle. Palmitoylation, a critical post-translational modification (PTM) primarily catalyzed by palmitoyltransferases of the zinc finger DHHC-type (ZDHHC), has recently demonstrated important implications in NSCLC. This review aims to elucidate the mechanisms and clinical potential of ZDHHC-mediated protein palmitoylation in NSCLC progression and immune escape.
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Humans ; Lipoylation ; Lung Neoplasms/pathology* ; Acyltransferases/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Animals

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Purpose To explore factors influencing vaginal delivery during the first stage of labor using intrapartum ultrasound and to construct predictive models for delivery decision-making.Materials and Methods A total of 473 nulliparous women admitted to Heping Hospital,Northern Theater General Hospital from July to December 2021 were prospectively enrolled as the training set.Clinical data on admission and fetal biometric parameters(biparietal diameter,femur length,head circumference and abdominal circumference)measured within one week before delivery were collected.Ultrasound assessments of fetal position,angle of progression(AOP)and head-perineum distance(HPD)were performed during the first stage of labor.The latent phase group(n=255)was subdivided into vaginal delivery group(n=186)and cesarean section group(n=69);the active phase group(n=218)was divided into vaginal delivery group(n=168)and cesarean section group(n=50).The associations between fetal position,AOP,HPD and vaginal delivery were analyzed,and predictive models were constructed for the latent phase(model 1)and active phase(model 2).A validation set of 547 women from January to September 2022 was used to evaluate model performance via area under the curve(AUC),calibration curves and decision curve analysis.Results In the latent phase,multivariate regression identified maternal height(OR=3.970,P=0.002),pre-pregnancy body mass index(OR=0.893,P=0.036),labor onset type(OR=2.415,P=0.045),neonatal birth weight(OR=3.728,P=0.002),AOP(OR=11.649,P<0.001)and HPD(OR=4.240,P=0.004)as significant predictors.The training and validation sets showed AUCs of 0.917 and 0.869,respectively.Goodness-of-fit tests indicated excellent model calibration(χ2=3.437,P=0.904;χ2=10.877,P=0.209).Decision curve analysis demonstrated strong clinical utility.For the active phase,significant predictors included maternal height(OR=6.532,P<0.001),neonatal birth weight(OR=11.890,P<0.001),fetal position(OR=4.600,P=0.003),AOP(OR=7.229,P<0.001)and HPD(OR=4.722,P=0.005).AUCs were 0.943(training)and 0.906(validation),with good calibration(χ2=4.340,P=0.740;χ2=9.836,P=0.277)and clinical applicability.Conclusion First stage ultrasound assessment of fetal position,AOP and HPD correlates with delivery outcomes.The developed nomogram models combining these parameters with clinical factors provide valuable guidance for delivery decision-making.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*