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 evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

AIM To investigate the in vivo pharmacokinetics of chlorogenic acid,isoquercetin,ferulic acid,isorhamnetin and shionone in Asteris Radix et Rhizoma in rats.METHODS Twelve rats were randomly assigned into 2 groups and given intragastric administration of conventional dose(0.63 g/kg)and large dose(3.3 g/kg)of Asteris Radix et Rhizoma extracts,respectively,after which blood collection was made at 0.083,0.167,0.33,0.5,0.75,1,1.5,2,4,6,8,12,24 h,UPLC-MS/MS was adopted in the plasma concentration determination of various effective constituents,and main pharmacokinetic parameters were calculated.RESULTS Various effective constituents in the large dose group demonstrated prolonged t1/2,MRT0-∞ as compared with those in the conventional dose group(P＜0.05).After dose correction,Cmax of chlorogenic acid,isoquercetin,shionone in the large dose group displayed no obvious changes(P＞0.05),while Cmax of ferulic acid,isorhamnetin,and AUC0-t,AUC0-∞ of various effective constituents were higher than those in the conventional dose group(P＜0.05).CONCLUSION Various effective constituents in the high dose of Asteris Radix et Rhizoma can maintain high-concentration and long-time effects on rat bladder tissue.

Objective To comprehensively investigate the subcomponent characteristics of inhibitory control for children with autism spectrum disorder(ASD)aged 4-5 years under experimental and natural environments.Methods Thirty children with ASD aged 4-5 years and 30 chronological-age and intellectual level-matched typically developing children were recruited.The Simon task,Go/nogo task,and Stroop task were used to examine the conflict response inhibition,prepotent response inhibition,and interference control subcomponents of inhibitory control,respectively.The inhibit subscale of the behavior rating inventory of executive function-preschool version was employed to assess children's inhibition in daily natural situations.Results Under the incongruent condition of the Simon task,there were no significant differences in mean reaction time and accuracy between ASD group and the control group(P>0.05).In the Go/nogo task,the ASD group demonstrated elevated false positive errors compared to the controls[3.10%(0,6.20%)vs.0(0,0.78%),P=0.005].However,there were no significant differences in mean reaction time and false alarm error between ASD group and the control group(P>0.05).In the Stroop task,there were no significant differences in the accuracy and mean reaction time between ASD group and the control group(P>0.05).Additionally,the ASD group scored significantly worse than the controls in the inhibit subscale of BRIEF-P[(60.47±9.63)vs.(54.23±7.45),P=0.007].Conclusions The inhibitory control of children with ASD aged 4-5 years are partially impaired in a structural experimental setting while severely deficient in a natural environment.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

Objective:To develop an artificial intelligence-based model for automated recognition of serum indices using machine vision and deep learning.Methods:This study was a cross-sectional study.Serum sample images were collected fromWest China Hospital of Sichuan University from September 21, 2020 to January 20, 2023 using the imaging device of the fully automated sample pre-processing system. A computer random number generator was used to randomly select one whole hour each day, and all serum sample images processed within that hour were included. After excluding samples with unqualified images and missing serum index results, a total of 5, 534 samples were included. These were divided into a training set and a test set in an 8∶2 ratio using Python random shuffle function, and 4, 458 samples were in the training set and 1, 076 samples were in the test set. After manual inspection, the serum regions were annotated using the MATLAB Image Labeler tool and converted into YOLO format, and a YOLO v5-based model was constructed for automatic serum region extraction. The actual values of lipemia index (L-index), hemolysis index (H-index), and icterus index (I-index) were measured using the automatic biochemical analyzerwith matched reagent kits. A serum index regression model was constructed based on the MobileNet v2 network using the PyTorch 1.10.0 framework. The grading performance of the model was evaluated using accuracy, Kappa coefficient, sensitivity, specificity, positive predictive value, and negative predictive value. Regression performance was assessed using root mean square error (RMSE), mean absolute error (MAE), coefficient of determination (R2), and Bland-Altman analysis.Results:The overall accuracy rates for grading L-index, H-index, and I-index were 98.88%, 95.26%, and 92.47%, respectively, with Kappa coefficients of 0.72, 0.72, and 0.59. For L-index, MAE was 5.11, RMSE was 9.77, and R2 was 0.78. For H-index, MAE was 5.18, RMSE was 8.99, and R2 was 0.89. For I-index, MAE was 1.13, RMSE was 3.01, and R2 was 0.71. Bland-Altman analysis showed that 95.5%, 95.1%, and 95.7% of the data points fell within the consistency intervals for L-index, H-index, and I-index, respectively.Conclusion:The study developed an artificial intelligence-based serum index regression modelto estimate serum indices with high efficiency and accuracy. It shows great potential for reducing laboratory costs, improving clinical testing efficiency, and promoting intelligent development in laboratory medicine.

Objective To comprehensively investigate the subcomponent characteristics of inhibitory control for children with autism spectrum disorder(ASD)aged 4-5 years under experimental and natural environments.Methods Thirty children with ASD aged 4-5 years and 30 chronological-age and intellectual level-matched typically developing children were recruited.The Simon task,Go/nogo task,and Stroop task were used to examine the conflict response inhibition,prepotent response inhibition,and interference control subcomponents of inhibitory control,respectively.The inhibit subscale of the behavior rating inventory of executive function-preschool version was employed to assess children's inhibition in daily natural situations.Results Under the incongruent condition of the Simon task,there were no significant differences in mean reaction time and accuracy between ASD group and the control group(P>0.05).In the Go/nogo task,the ASD group demonstrated elevated false positive errors compared to the controls[3.10%(0,6.20%)vs.0(0,0.78%),P=0.005].However,there were no significant differences in mean reaction time and false alarm error between ASD group and the control group(P>0.05).In the Stroop task,there were no significant differences in the accuracy and mean reaction time between ASD group and the control group(P>0.05).Additionally,the ASD group scored significantly worse than the controls in the inhibit subscale of BRIEF-P[(60.47±9.63)vs.(54.23±7.45),P=0.007].Conclusions The inhibitory control of children with ASD aged 4-5 years are partially impaired in a structural experimental setting while severely deficient in a natural environment.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*