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.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective To investigate residents'willingness to use"internet+nursing services"of a community in Xiamen City and provide reference for the code of practice to promote the service.Methods A total of 350 community residents in Xiamen City were investigated by convenience sampling from January to December 2023.The questionnaire was self-designed with regard to their willingness to use"internet+nursing services".Results 336 questionnaires were effectively collected.The total score of willingness to use"internet+nursing services"of community residents in Xiamen City was(68.80±8.73)points,but only 19.6％of residents knew about"internet+nursing services".There were statistically significant differences in willingness to use among community residents with different ages,medical payment type,whether they knew"internet+nursing services"or not,and the number of service items needed(P＜0.05).Among them,age,whether they knew"internet+nursing services"or not and the number of service items needed were the main influencing factors of willingness to use(P＜0.05).Conclusion Community residents in Xiamen City show above the middle level of willingness to use"internet+nursing services".However,the popularity of"internet+nursing services"has a large room for improvement.The publicity to the residents should be strengthened,and the care needs of residents with different demographic characteristics should be considered.The supporting application functions of such platforms should be designed to meet the health needs of community residents,especially elderly patients with great demand for services.

Objective:To evaluate the effectiveness of a rotation training program for primary care general practitioners (GPs) in Taizhou, China, designed around three core competencies.Methods:A longitudinal study was conducted. A total of 111 primary care GPs participating in the 1st to 5th sessions of the Taizhou GP rotation training program at Taizhou Hospital (the designated training center) in Zhejiang Province from July 2022 to December 2024 were included. Based on the World Organization of Family Doctors (WONCA) competency model, combined with literature review and expert consultation, 15 potential training components were identified. A needs assessment survey among primary care GPs was then conducted, leading to the finalization of three core competencies for the training: ①Evidence-based management of common diseases, frequently-occurring diseases, and common symptoms; ②Early identification, management, and referral of critically ill patients; ③Chronic disease management and health promotion capabilities. A 4-month full-time immersion training program was structured around these competencies, comprising three phases: theoretical training (1 week), clinical comprehensive skills training (14 weeks), and primary care practice training (1 week). Assessments included a pre-and post-training theoretical knowledge test and a final clinical assessment. The final assessment utilized a three-station Objective Structured Clinical Examination (OSCE) evaluating patient consultation, clinical reasoning & decision-making, and clinical procedural skills. A self-administered satisfaction survey was also distributed post-training.Results:The 111 participants were predominantly aged 30-49 years (72.1% (80/111)), held bachelor′s degrees (87.4% (97/111)), were licensed physicians (78.4% (87/111)), and had junior or intermediate professional titles (87.4% (97/111)). Post-training theoretical scores were significantly higher than pre-training scores (76.26±7.00 vs. 69.94±6.40, t=-10.45, P<0.001). All participants 100%(111/111) passed the final OSCE assessment. The mean scores for the OSCE stations were: patient consultation 85.99±7.30, clinical reasoning & decision-making 82.72±7.61, and clinical procedural skills 89.60±5.65. Satisfaction rates were 100.0% (111/111) for the overall program, the three-phase design, the core competency training content, theoretical training, clinical skills training, and clinical rotation departments. Satisfaction was 98.2% (109/111) for the 4-month full-time duration, 99.1% (110/111) for the "2+X" clinical rotation model (2 weeks each in General Practice and Emergency Medicine+elective rotations in 4 other departments), and 97.3% (108/111) for the primary care practice base. Conclusions:The competency-based rotation training program for primary care GPs in Taizhou effectively enhanced participants′ theoretical knowledge and clinical practical skills, and achieved high levels of participant satisfaction. This model offers valuable insights for optimizing primary care GP training in similar settings.

Objective To investigate the protective effect of LncRNA MEG3 on the retina in early-stage diabetic rats through regulation of the COX-2/PGE2/VEGF signaling pathway.Methods 50 male SD rats of SPF grade were selected for the study.Among them,10 rats were assigned to the control group,while 40 rats were used to establish diabetic retinopathy models.A total of 32 rats successfully underwent modeling and were subsequently divided into four groups(n=8 per group):model group,negative control group,MEG3 overexpression group,and MEG3 overexpression+COX-2 inhibitor group.Histopathological changes,vascular permeability,glucose and lipid metabolism,inflammatory factors,oxidative stress indices,PGE2 levels,as well as the relative mRNA and protein expression levels of COX-2 and VEGF were evaluated in each group.Results Compared with the control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly decreased,whereas the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly increased in the model group(P<0.05).Compared with the negative control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly increased in the MEG3 overexpression group,while the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly decreased(P<0.05).Compared with the MEG3 overexpression group,HDL-C,CAT,GSH-PX,and SOD levels were further increased in the MEG3 overexpression+COX-2 inhibitor group,and the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were further decreased(P<0.05).Conclusion LncRNA MEG3 is capable of regulating the COX-2/PGE2/VEGF pathway,enhancing glucose and lipid metabolism in rats,suppressing the expression of inflammatory factors,attenuating stress responses,and alleviating diabetic retinopathy.

Anticipatory anxiety is a negative emotion that arises when individuals encounter potential threats or uncertainties in the future. It is the core symptom of a variety of anxiety disorders, and is closely associated with the occurrence, severity, treatment outcome, and prognosis of anxiety disorders, which has garnered a growing amount of focus in clinical practice. Nevertheless, scientific research on anticipatory anxiety continues to face obstacles such as unclear pathological mechanisms, the absence of simple and consistent self-assessment tools, and effective interventions. To improve understanding of the role of anticipatory anxiety in the diagnosis and treatment of anxiety disorders, this study reviews pertinent domestic and international literature, and briefly introduces the concept, assessment and measurement, activation paradigm, pathological mechanisms, and interventions of anticipatory anxiety.

Objective To investigate the protective effect of LncRNA MEG3 on the retina in early-stage diabetic rats through regulation of the COX-2/PGE2/VEGF signaling pathway.Methods 50 male SD rats of SPF grade were selected for the study.Among them,10 rats were assigned to the control group,while 40 rats were used to establish diabetic retinopathy models.A total of 32 rats successfully underwent modeling and were subsequently divided into four groups(n=8 per group):model group,negative control group,MEG3 overexpression group,and MEG3 overexpression+COX-2 inhibitor group.Histopathological changes,vascular permeability,glucose and lipid metabolism,inflammatory factors,oxidative stress indices,PGE2 levels,as well as the relative mRNA and protein expression levels of COX-2 and VEGF were evaluated in each group.Results Compared with the control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly decreased,whereas the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly increased in the model group(P<0.05).Compared with the negative control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly increased in the MEG3 overexpression group,while the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly decreased(P<0.05).Compared with the MEG3 overexpression group,HDL-C,CAT,GSH-PX,and SOD levels were further increased in the MEG3 overexpression+COX-2 inhibitor group,and the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were further decreased(P<0.05).Conclusion LncRNA MEG3 is capable of regulating the COX-2/PGE2/VEGF pathway,enhancing glucose and lipid metabolism in rats,suppressing the expression of inflammatory factors,attenuating stress responses,and alleviating diabetic retinopathy.

Objective To investigate residents'willingness to use"internet+nursing services"of a community in Xiamen City and provide reference for the code of practice to promote the service.Methods A total of 350 community residents in Xiamen City were investigated by convenience sampling from January to December 2023.The questionnaire was self-designed with regard to their willingness to use"internet+nursing services".Results 336 questionnaires were effectively collected.The total score of willingness to use"internet+nursing services"of community residents in Xiamen City was(68.80±8.73)points,but only 19.6％of residents knew about"internet+nursing services".There were statistically significant differences in willingness to use among community residents with different ages,medical payment type,whether they knew"internet+nursing services"or not,and the number of service items needed(P＜0.05).Among them,age,whether they knew"internet+nursing services"or not and the number of service items needed were the main influencing factors of willingness to use(P＜0.05).Conclusion Community residents in Xiamen City show above the middle level of willingness to use"internet+nursing services".However,the popularity of"internet+nursing services"has a large room for improvement.The publicity to the residents should be strengthened,and the care needs of residents with different demographic characteristics should be considered.The supporting application functions of such platforms should be designed to meet the health needs of community residents,especially elderly patients with great demand for services.

Objective:To evaluate the effectiveness of a rotation training program for primary care general practitioners (GPs) in Taizhou, China, designed around three core competencies.Methods:A longitudinal study was conducted. A total of 111 primary care GPs participating in the 1st to 5th sessions of the Taizhou GP rotation training program at Taizhou Hospital (the designated training center) in Zhejiang Province from July 2022 to December 2024 were included. Based on the World Organization of Family Doctors (WONCA) competency model, combined with literature review and expert consultation, 15 potential training components were identified. A needs assessment survey among primary care GPs was then conducted, leading to the finalization of three core competencies for the training: ①Evidence-based management of common diseases, frequently-occurring diseases, and common symptoms; ②Early identification, management, and referral of critically ill patients; ③Chronic disease management and health promotion capabilities. A 4-month full-time immersion training program was structured around these competencies, comprising three phases: theoretical training (1 week), clinical comprehensive skills training (14 weeks), and primary care practice training (1 week). Assessments included a pre-and post-training theoretical knowledge test and a final clinical assessment. The final assessment utilized a three-station Objective Structured Clinical Examination (OSCE) evaluating patient consultation, clinical reasoning & decision-making, and clinical procedural skills. A self-administered satisfaction survey was also distributed post-training.Results:The 111 participants were predominantly aged 30-49 years (72.1% (80/111)), held bachelor′s degrees (87.4% (97/111)), were licensed physicians (78.4% (87/111)), and had junior or intermediate professional titles (87.4% (97/111)). Post-training theoretical scores were significantly higher than pre-training scores (76.26±7.00 vs. 69.94±6.40, t=-10.45, P<0.001). All participants 100%(111/111) passed the final OSCE assessment. The mean scores for the OSCE stations were: patient consultation 85.99±7.30, clinical reasoning & decision-making 82.72±7.61, and clinical procedural skills 89.60±5.65. Satisfaction rates were 100.0% (111/111) for the overall program, the three-phase design, the core competency training content, theoretical training, clinical skills training, and clinical rotation departments. Satisfaction was 98.2% (109/111) for the 4-month full-time duration, 99.1% (110/111) for the "2+X" clinical rotation model (2 weeks each in General Practice and Emergency Medicine+elective rotations in 4 other departments), and 97.3% (108/111) for the primary care practice base. Conclusions:The competency-based rotation training program for primary care GPs in Taizhou effectively enhanced participants′ theoretical knowledge and clinical practical skills, and achieved high levels of participant satisfaction. This model offers valuable insights for optimizing primary care GP training in similar settings.

Anticipatory anxiety is a negative emotion that arises when individuals encounter potential threats or uncertainties in the future. It is the core symptom of a variety of anxiety disorders, and is closely associated with the occurrence, severity, treatment outcome, and prognosis of anxiety disorders, which has garnered a growing amount of focus in clinical practice. Nevertheless, scientific research on anticipatory anxiety continues to face obstacles such as unclear pathological mechanisms, the absence of simple and consistent self-assessment tools, and effective interventions. To improve understanding of the role of anticipatory anxiety in the diagnosis and treatment of anxiety disorders, this study reviews pertinent domestic and international literature, and briefly introduces the concept, assessment and measurement, activation paradigm, pathological mechanisms, and interventions of anticipatory anxiety.