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.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Aging is the result of the accumulation of various molecular and cellular damages over time,encompassing 12 characteristic hallmarks divided into three categories.These include primary hallmarks such as genomic instability,telomere attrition,epigenetic alterations,loss of proteostasis,and disabled macroautophagy;antagonistic hallmarks like deregulated nutrient sensing,mitochondrial dysfunction,and cellular senescence;and integrative hallmarks including stem cell exhaustion,altered intercellular com-munication,chronic inflammation and dysbiosis.Therefore,investigating cellular signaling factors within a single pathway is insufficient to comprehensively understand the complex mechanisms underlying aging.Casein kinase Ⅱ(CK2),one of the earliest identified protein kinases,is capable of phosphorylating ser-ine/threonine/tyrosine residues on hundreds of substrates.It exhibits highly constitutive expression and activity,and is extensively involved in the regulation of cellular processes such as proliferation,differenti-ation,apoptosis,stress response,metabolism,and immune function.CK2 plays a unique role in coordi-nating the cross-talk and integration of various signaling pathways,which is crucial for maintaining cell survival and homeostasis.Recent studies have revealed that CK2 exhibits perturbations in both expression levels and enzymatic activity during aging process,with notable heterogeneity observed across different animals,tissues and cellular models.Overall,the downregulation of CK2 expression not only promotes the development of primary hallmarks but also alleviates antagonistic hallmarks and ameliorates integrative hallmarks of aging,demonstrating dual effect and interconnected mechanisms.Notably,aberrant activa-tion in CK2 expression and activity are associated with various aging-related diseases,including cancer,cardiovascular diseases,chronic metabolic disorders,neurodegenerative diseases and skeletal degenera-tive conditions.Therefore,maintaining CK2 homeostasis may represent an effective strategy for delaying aging.This review summarizes the latest advances in CK2 and aging research,providing not only deeper insights into the common mechanisms underlying aging and aging-related diseases,but also a theoretical foundation for identifying potential targets for the early prevention of aging-related diseases.

Aging is the result of the accumulation of various molecular and cellular damages over time,encompassing 12 characteristic hallmarks divided into three categories.These include primary hallmarks such as genomic instability,telomere attrition,epigenetic alterations,loss of proteostasis,and disabled macroautophagy;antagonistic hallmarks like deregulated nutrient sensing,mitochondrial dysfunction,and cellular senescence;and integrative hallmarks including stem cell exhaustion,altered intercellular com-munication,chronic inflammation and dysbiosis.Therefore,investigating cellular signaling factors within a single pathway is insufficient to comprehensively understand the complex mechanisms underlying aging.Casein kinase Ⅱ(CK2),one of the earliest identified protein kinases,is capable of phosphorylating ser-ine/threonine/tyrosine residues on hundreds of substrates.It exhibits highly constitutive expression and activity,and is extensively involved in the regulation of cellular processes such as proliferation,differenti-ation,apoptosis,stress response,metabolism,and immune function.CK2 plays a unique role in coordi-nating the cross-talk and integration of various signaling pathways,which is crucial for maintaining cell survival and homeostasis.Recent studies have revealed that CK2 exhibits perturbations in both expression levels and enzymatic activity during aging process,with notable heterogeneity observed across different animals,tissues and cellular models.Overall,the downregulation of CK2 expression not only promotes the development of primary hallmarks but also alleviates antagonistic hallmarks and ameliorates integrative hallmarks of aging,demonstrating dual effect and interconnected mechanisms.Notably,aberrant activa-tion in CK2 expression and activity are associated with various aging-related diseases,including cancer,cardiovascular diseases,chronic metabolic disorders,neurodegenerative diseases and skeletal degenera-tive conditions.Therefore,maintaining CK2 homeostasis may represent an effective strategy for delaying aging.This review summarizes the latest advances in CK2 and aging research,providing not only deeper insights into the common mechanisms underlying aging and aging-related diseases,but also a theoretical foundation for identifying potential targets for the early prevention of aging-related diseases.

Objective:To investigate the host and vector composition of pestis and the epidemic situation of pestis among animals in the border port areas of Longchuan County, Yunnan Province.Methods:In September 2022, a survey was conducted on rodents and their surface parasitic fleas in the border port areas of Longchuan County, according to three habitat types: residential areas, agricultural areas, and forest-shrubbery areas. Samples of murine animals organs and their surface parasitic fleas were collected for isolation and identification of Yersinia pestis. Blood samples of plague indicating animals, such as murine animals, dogs and cats were collected, and serum plague F1 antibody was detected by indirect hemagglutination assay. Meanwhile, a retrospective investigation was conducted on the occurrence of self dead rats, sick rats, and suspected cases in the local area from 2018 to 2022 through interviews with farmers. Results:A total of 168 murine animals belonging to 3 orders, 5 families, 10 genera, and 11 species were captured in three habitats in Longchuan County. Among them, the capture rate in residential areas was 5.00% (30/600), with Rattus tanezumi and Suncus murinus as dominant species, with a composition ratio of 50.00% (15/30). The capture rate in agricultural areas was 9.67% (122/1 262), with Rattus tanezumi and Suncus murinus as dominant species, with a composition ratio of 50.82% (62/122) and 44.26% (54/122), respectively. The capture rate in the forest-shrubbery areas was 6.25% (16/256), with Hylomys suillus and Eothenomys eleusis as dominant species, with a composition ratio of 37.50% (6/16) and 31.25% (5/16), respectively. Among the captured murine animals, 20 individuals carried 52 parasitic fleas, belonging to 2 species of 2 genera and 2 families. The total flea infection rate was 11.90% (20/168), and the total flea index was 0.31 (52/168). The dominant specie was Xenopsylla cheopis (90.38%, 47/52). The flea infection rate in residential areas was 33.33% (10/30), and the flea index was 1.23 (37/30). The flea infection rate in agricultural areas was 7.38% (9/122), and the flea index was 0.11 (14/122). The flea infection rate in the forest-shrubbery areas was 6.25% (1/16), and the flea index was 0.06 (1/16). The samples of murine animals and their parasitic fleas obtained were isolated and cultured by Yersinia pestis, and the results were negative. A total of 144 serum samples from murine animals, dogs and cats were separated, and no F1 antibody against pestis was detected. According to interviews and investigations, no abnormal situations such as a large number of self dead rats, sick rats, and suspected cases were found from 2018 to 2022. Conclusions:No plague epidemic has been found in the border port areas of Longchuan County recently. The main host of plague, Rattus tanezumi, and the main vector, Xenopsylla cheopis, remain the dominant species in this area.

Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.

Objective To explore the application effect of outpatient 5G guided wristbands in reducing medical obstacles for the aged and improving service experience,and provide evidence for their promotion and application.Method A total of 216 aged patients who visited our hospital's outpatient department from January to December 2022 were selected as the research subjects.They were divided into a control group and an trial group based on the parity of the last digits of their medical card numbers,with 108 patients in each group.Patients in the trial group received 5G guided hand ring intervention on the basis of traditional guidance,while patients in the control group received traditional guidance methods.The arrival time and emergency response time of patients medical experience,and satisfaction with medical treatment were compared between the two groups of patients.Results The arrival time and emergency response time of patients in the trial group were shorter than those in the control group;The trial group had better scores in all six dimensions of medical experience than those of the control group;excepting the medical environment and health conditions,the clarity of the outpatient department distribution route map and the service of the triage staff,the ease of registration,waiting time for medical treatment,and overall satisfaction of patients in the trial group were better than those in the control group,and the difference between the two groups was statistically significant(all P<0.05).Conclusion The outpatient 5G guided wristband can improve the efficiency of handling sudden problems and the medical experience for elderly patients,thereby increasing patient satisfaction.

Objective To analyze the changing trend of the disease burden of age-related macular degeneration(AMD)in China from 1990 to 2021 and the impact of age,period,and cohort effects,and to predict the standardized prev-alence and disability-adjusted life year(DALY)rate of AMD in China from 2022 to 2035.Methods The data on the preva-lence of AMD,the number of AMD patients,DALYs,and DALY rates in China from 1990 to 2021 were obtained from the Global Burden of Disease(GBD 2021).The segmented regression model was used to analyze the trend changes in the prev-alence and DALY of patients with AMD in China,the age-period-cohort(APC)model was employed to estimate the age,period,and cohort effects related to the prevalence risk and DALY risk of AMD,and the Bayesian age-period cohort model was used to analyze the standardized prevalence and DALY rate of AMD in China from 2022 to 2035.Results Compared with 1990,the number of AMD patients and the prevalence of this disease in China in 2021 increased by 199.94％and 148.02％,respectively,and the DALYs and DALY rate increased by 183.95％and 134.80％,respectively,with the higher value of relevant indicators observed in females compared with males.From 1990 to 2021,the standardized prevalence of AMD in China showed an increasing trend,with the average annual percentage change(AAPC)being 0.17％.In contrast,the standardized DALY rate of AMD showed a decreasing trend,with the AAPC being-0.03％.The results of the age-peri-od-cohort model showed that the longitudinal age curves for both the prevalence and DALY rate of AMD in China showed an increasing and then decreasing trend,peaking at 85-89 years of age.Over time,the prevalence risk of AMD increased and then decreased,while the DALY risk continued to decline.The birth cohort analysis results showed that the overall fluctua-tion of the AMD prevalence risk cohort effect in China was small,with a decline first and then a fluctuating increase.Mean-while,the DALY risk gradually decreased as the birth cohort moved backward.It can be predicted that both the standard-ized prevalence and the standardized DALY rate of AMD may present an upward trend in China from 2022 to 2035.Conclu-sion From 1990 to 2021,the standardized prevalence of AMD in China displays an upward trend,while its standardized DALY rate exhibits a downward trend.Notably,the disease burden is more pronounced in the female population compared with the male population.With the continued aging of the population,it can be predicted that both the standardized preva-lence and DALY rate of AMD will escalate from 2022 to 2035.This finding underscores the need for targeted interventions,particularly for elderly women.Meanwhile,it is necessary to enhance health education for the whole population and formu-late effective public health policies to alleviate the disease burden associated with AMD in China.