Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To explore the effect of hypoxia-inducible factor-1α(HIF-1α)inhibitor LW6 on ferroptosis in septic cardiomyopathy rats.Methods Rat septic cardiomyopathy model was prepared using cecal ligation and puncture(CLP)method.Thirty-six specific pathogen-free(SPF)6-8 weeks male SD rats were randomly divided into the sham-operated group,CLP group,CLP+solvent group,LW6 group,ferrostatin-1(Fer-1)group,and LW6+Fer-1 group.The degree of myocardial damage in each group was evaluated through hematoxylin-eosin stai-ning and detection of lactate dehydrogenase and creatine kinase content in cardiac tissue.Myocardial mitochondrial damage was observed by transmission electron microscopy.Ferroptosis level was determined by detecting iron ion concentration,reduced glutathione,malondialdehyde,and reactive oxygen species.Protein expression levels of HIF-1α,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in cardiac tissue were detected by Western blotting.Results Compared with the CLP group and the CLP+solvent group,the LW6 group could ameliorate myocardial damage,alleviate mitochondrial damage,inhibit ferroptosis-related indicators(all P＜0.05),reduce HIF-1α protein expression levels(P＜0.05),and enhance SLC7A11 and GPX4 protein expression levels(both P＜0.05).Conclusion LW6 decreases HIF-1α expression and ferroptosis levels through the SLC7A11/GPX4 pathway,and ameliorates sepsis-induced cardiomyopathy.

Objective To analyze the deployment of policy instruments and the distribution of stakeholder engagement in provincial policies on nursing assistant training and management.Methods The relevant policy texts on nursing assistant training and management were systematically searched and collected from the official websites of provincial governments and their direct departments,CNKI,and the PKU Law Database.A two-dimensional framework of policy instruments-stakeholder was constructed,and the content analysis was used to classify,encode and quantify policy clauses.Results The study encompassed 20 provincial-level nursing assistant training and management policies,yielding a total of 359 codes.Within the policy instruments dimension,environmental,supply,and demand instruments constituted 66.30％,28.97％,and 4.74％,respectively.In terms of stakeholders,the management-side accounted for 56.55％,providers and trainers for 18.11％each,partners for 5.01％,and demand-side for 2.23％.Both management-side and trainers engaged with 3 policy instruments,providers with 2,and partners and demand-side with one each.Conclusion In the provincial nursing assistant training and management policies,there are differences in the deployment of policy instruments,and the distribution of stakeholders is uneven.Managers should pay attention to publicity guidance and platform construction,improve incentive mechanisms and training programs,and innovate cooperation models with stakeholders,as well as strengthen communication and exchange.

Objective To explore the effect of hypoxia-inducible factor-1α(HIF-1α)inhibitor LW6 on ferroptosis in septic cardiomyopathy rats.Methods Rat septic cardiomyopathy model was prepared using cecal ligation and puncture(CLP)method.Thirty-six specific pathogen-free(SPF)6-8 weeks male SD rats were randomly divided into the sham-operated group,CLP group,CLP+solvent group,LW6 group,ferrostatin-1(Fer-1)group,and LW6+Fer-1 group.The degree of myocardial damage in each group was evaluated through hematoxylin-eosin stai-ning and detection of lactate dehydrogenase and creatine kinase content in cardiac tissue.Myocardial mitochondrial damage was observed by transmission electron microscopy.Ferroptosis level was determined by detecting iron ion concentration,reduced glutathione,malondialdehyde,and reactive oxygen species.Protein expression levels of HIF-1α,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in cardiac tissue were detected by Western blotting.Results Compared with the CLP group and the CLP+solvent group,the LW6 group could ameliorate myocardial damage,alleviate mitochondrial damage,inhibit ferroptosis-related indicators(all P＜0.05),reduce HIF-1α protein expression levels(P＜0.05),and enhance SLC7A11 and GPX4 protein expression levels(both P＜0.05).Conclusion LW6 decreases HIF-1α expression and ferroptosis levels through the SLC7A11/GPX4 pathway,and ameliorates sepsis-induced cardiomyopathy.

Relevant China's literature on the application of brain-computer interface technology in the field of rehabilita-tion of stroke patients was retrieved in the China Knowledge Network database from its establishment to December 31,2024,and CiteSpace visual analysis software was used to analyze the selected literature in terms of trend of annual publica-tion number,author collaboration network,keyword co-occurrences and emergences and to generate a corresponding knowledge map.It's pointed out brain-computer interface technology showed significant application potential for motor function recovery and neurorehabilitation,which had the research hotspots of the cross technologies covering motor imagina-tion,rehabilitation training and virtual reality and the research frontiers of the fusion application of intelligent algorithms of deep learning and pattern recognition.The challenges and future development directions of the field were investigated,and references were provided for promoting the application of brain-computer interface technology to rehabilitation of sroke patients in China.[Chinese Medical Equipment Journal,2025,46(9):65-69]

Relevant China's literature on the application of brain-computer interface technology in the field of rehabilita-tion of stroke patients was retrieved in the China Knowledge Network database from its establishment to December 31,2024,and CiteSpace visual analysis software was used to analyze the selected literature in terms of trend of annual publica-tion number,author collaboration network,keyword co-occurrences and emergences and to generate a corresponding knowledge map.It's pointed out brain-computer interface technology showed significant application potential for motor function recovery and neurorehabilitation,which had the research hotspots of the cross technologies covering motor imagina-tion,rehabilitation training and virtual reality and the research frontiers of the fusion application of intelligent algorithms of deep learning and pattern recognition.The challenges and future development directions of the field were investigated,and references were provided for promoting the application of brain-computer interface technology to rehabilitation of sroke patients in China.[Chinese Medical Equipment Journal,2025,46(9):65-69]

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P＜0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P＜0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.