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.

Background: As Taiwan’s population ages, falls among older adults have become a critical public health concern. However, limited data exist regarding temporal trends and injury patterns in fall-related emergency department (ED) visits. This study aimed to examine trends in fall-related ED visits and hospitalizations among older adults in Taiwan and to explore injury distributions by age group. Methods: We conducted a retrospective cohort study using data from the National Taiwan University Hospital between 2011 and 2017. Patients aged ≥65 years were compared with those aged 20–64 years. Fall-related visits were identified using chief complaints and the International Classification of Diseases 9th/10th revision (ICD-9/ICD-10) codes. Outcomes included hospitalization rates, length of stay, and 30-day mortality. Results: A total of 22,471 fall-related ED visits were analyzed. While visits among younger adults declined (annual growth rate, -1.34%), visits among older adults increased (2.37% annually), with the steepest rise in those aged ≥85 years. Hospitalization occurred in 27.1% of older adults, nearly double that of younger adults (14.4%). Older adults also had longer hospital stays and higher 30-day mortality rates, findings consistent even when restricted to lower limb fractures. Conclusion Fall-related ED visits and hospitalizations are rising disproportionately among Taiwan’s older population. Targeted prevention strategies and transitional care interventions are urgently needed to address the growing clinical and economic burden of falls in aging societies.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To conduct a study on pricing by service unit to address the problems of hospice and palliative care pricing and fee system in China.Methods:Combining theoretical research and empirical evidence,this study organized the pricing mechanism of initiative hospice and palliative care services and established a graded and categorized pricing strategy.Empirical research was conducted based on real-world data from 36 pilot institutions in typical areas.Results:This study developed a comprehensive pricing framework for value-based classification price standard of initiative hospice and palliative care services from the perspective of incentive regulation.We proposed a pricing plan based on service units,with inpatient bed fee ranging from 459 to 606 yuan or 459 to 1 102 yuan,and home visit fee ranging from 89 to 264 yuan.Conclusions and suggestions:This study proposes a pricing scheme based on the technique and service value with a gradient fluctuation by service unit,and forms a set of price standards with high economic and technical feasibility,which can provide scientific evidences for solving the pricing problem of hospice care.In addition,there is still a need to establish a multi-level incentive compensation mechanism to motivate all levels and types of organisations and healthcare provider,and to promote the high-quality and sustainable development of hospice and palliative care.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.