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 and purpose:According to the latest data from the National Cancer Center,the incidence rate and mortality of lung cancer in China rank first among all malignant tumors,and 85%are non-small cell lung cancer(NSCLC).In recent years,immunotherapy based on programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)immune checkpoint inhibitors(ICIs)has made breakthrough progress in lung cancer,bringing more survival benefits to lung cancer patients.This study aimed to evaluate the cost-effectiveness of three major PD-L1 testing assays in guiding immunotherapy for patients with NSCLC,and to provide empirical evidence to guide the selection of cost-effective diagnosis and ICIs monotherapy regimens for NSCLC patients in China.Methods:From a healthcare system perspective,a decision-tree model was constructed to simulate the cost and effectiveness(percentage of the patients who were successfully diagnosed and who were correctly prescribed and underwent correct treatment according to China treatment guidelines)of employing Ventana PD-L1 IHC(SP263)assay,PD-L1 IHC 22C3 pharmDx,and Dako 22C3 antibody concentrate in early to mid-stage and advanced NSCLC patients in China,respectively.The cost-effectiveness of SP263 assay compared to other testing methods was assessed through the incremental analysis.The robustness of the base case analysis results was validated by using one-way sensitivity analysis and probabilistic sensitivity analysis.Results:When considering atezolizumab monotherapy following chemotherapy for early to mid-stage(Ⅱ A-Ⅲ B)NSCLC patients,in comparison to the 22C3 assay or 22C3 antibody concentrate,the SP263 assay incurred an additional cost of 9 449 yuan per successfully diagnosed and treated patient.The SP263 assay,which can guide multiple ICIs monotherapies(e.g.,atezolizumab,pembrolizumab)for advanced(Ⅳ)NSCLC patients,was dominant by achieving a higher percentage of successfully diagnosed and treated patients at a lower cost compared to Dako 22C3 assay and Dako 22C3 antibody concentrate.One-way sensitivity analysis and probabilistic sensitivity analysis both confirmed the robustness of the results.Conclusion:The Ventana PD-L1 IHC SP263 assay was cost-effective,compared to Dako PD-L1 IHC 22C3 assay and Dako 22C3 antibody concentrate for the immunotherapy treatment for both stage Ⅱ A-Ⅲ B and stage Ⅳ NSCLC patients in China.

OBJECTIVE: To systematically evaluate the effect and safety of the combination of Compound Xuanju Capsules (CXC) and Western medicine (WM) in the treatment of type Ш prostatitis complicated by ED. METHODS: We searched for randomized controlled trials (RCT) on the treatment of type Ш prostatitis complicated by ED with CXC+WM or WM in the Chinese and English databases CNKI, VIP, Wanfang Digital, Duxiu Academic Search and Chaoxing Electronic Book Information Retrieval, Fangzheng Apabi Electronic Book, Google Scholar Search, Web of Science, Scopus, PubMed, and others from their establishment to April 2024. According to the Cochrane Handbook requirement, we subjected the identified RCTs to meta-analysis using the RevMan 5.3 software. RESULTS: A total of 16 eligible studies were identified, involving 742 cases treated by combination therapy of CXC+WM and another 742 with WM alone. The results of meta-analysis showed that the rate of clinical effectiveness was dramatically higher in the CXC+WM than in the WM group (P<0.01, MD = 6.19, 95% CI: 4.63－8.28), and so were the IIEF-5 scores (P < 0.004, MD = 2.90, 95% CI: 0.90－4.89), while the quality of life (QOL) scores were significantly lower in the former group than in the latter (P<0.01, MD = －1.94, 95% CI: －2.47－－1.40), and so were the NIH-CPSI scores (P<0.01, MD = －3.92, 95% CI: －4.94－－2.91). No statistically significant difference was reported in the adverse reactions between the two groups (P = 0.12, MD = 0.03, 95% CI: －0.01－0.08). Publication bias analysis on the effectiveness rate of the results revealed an incomplete symmetry between the two sides of the funnel plot, indicating the possibility of publication biases. CONCLUSION The combination therapy of CXC+WM is superior to WM alone in the treatment of type Ш prostatitis complicated by ED for its high safety and effect of improving the patients' erectile function, but inferior to the latter in improving the QOL and NIH-CPSI scores of the patients.
Male ; Humans ; Prostatitis/complications* ; Erectile Dysfunction/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Capsules ; Randomized Controlled Trials as Topic ; Drug Therapy, Combination ; Treatment Outcome ; Quality of Life ; Phytotherapy

The pathological mechanisms and related physiological indicators of acute mountain sickness(AMS)were introduced,and the present situation of wearable devices applied in AMS auxiliary detection and diagnosis were reviewed.The challenges and future development directions of wearable devices applied in auxiliary detection and diagnosis were pointed out.[Chinese Medical Equipment Journal,2025,46(9):100-107]

OBJECTIVE: To explore the clinical efficacy and safety of the "Three-Step Nine-Method Lumbar Correction" combined with physical therapy in the treatment of patients with degenerative lumbar spondylolisthesis(DLS). METHODS: From January 2021 to December 2021, 72 patients diagnosed with DLS were enrolled and divided into the Three-Step Nine-Method Lumbar Correction group and the pelvic traction group, with 36 cases in each group. In the Three-Step Nine-Method Lumbar Correction group, there were 15 males and 21 females;aged 54 to 66 years old, with an average of (59.07±5.69) years old;the course of disease was 14 to 26 years old, with an average of (20.35±5.66) years old. They were treated with the Three-Step Nine-Method Lumbar Correction combined with low-frequency physical therapy, 3 times a week, for a 4-week course. In the pelvic traction group, there were 12 males and 24 females;aged 54 to 66 years old, with an average of (59.69±5.59) years old;the course of disease was 13 to 26 years old, with an average of (19.74±5.80) years old. They were treated with pelvic traction combined with low-frequency physical therapy. Efficacy evaluation was conducted using the visual analogue scale(VAS), Oswestry disability index(ODI), Japanese Orthopaedic Association (JOA) score, and Short Form 36 Health Survey (SF-36) before treatment, after 2 and 4 weeks of treatment, and at the 8-week follow-up after the end of treatment. In addition, imaging parameters of paravertebral muscles were evaluated before treatment and at the completion of treatment. RESULTS: All 72 patients completed the follow-up for 8 weeks. At the 8-week follow-up after the end of treatment, in the Three-Step Nine-Method Lumbar Correction group, the VAS score for low back pain decreased from (6.25±1.23) points before treatment to (1.25±0.65) points, with a statistically significant difference (P<0.05);the ODI decreased from (57.17±7.13)% before treatment to (19.89±5.66)%, with a statistically significant difference (P<0.05);the JOA score and SF-36 score increased from (15.46±3.20) points and (35.25±9.28) points before treatment to (23.75±2.10) points and (62.31±13.03) points, respectively, with statistically significant differences (P<0.05). The improvement of each index in the Three-Step Nine-Method Lumbar Correction group was better than that in the pelvic traction group (P<0.05), but the change in imaging parameters was not significant (P>0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05), and no serious adverse events occurred. CONCLUSION The Three-Step Nine-Method Lumbar Correction combined with physical therapy has a definite efficacy in the treatment of DLS. It can significantly relieve pain symptoms, improve physical function and patients' quality of life. Its effect is better than that of pelvic traction combined with physical therapy, and it has high safety. However, its improvement on paravertebral muscles is not obvious.
Humans ; Male ; Female ; Middle Aged ; Spondylolisthesis/physiopathology* ; Aged ; Prospective Studies ; Lumbar Vertebrae/physiopathology* ; Physical Therapy Modalities ; Adult

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Objective To propose a centrifuge overload simulation method for post stall super manueuvering flights to conduct the pilot centrifuge training during post stall super maneuvering flights.Methods Firstly,the independent active disturbance rejection control was designed in the longitudinal,transverse and heading channels to achieve closed-loop control of the aircraft at high angles of attack with thrust vector control technology.Secondly,a method for establishing control command for the three-axis centrifuge with the main arm rotation,cabin roll and cabin pitch was put forward based on the relationship between the pilot overload and the centrifuge control information.Finally,a simulation model was constructed based on the cobra maneuver to carry out digital simulation experiments.Results The method proposed effectively extracted overload information under super maneuvering flight conditions,then the centrifuge control commands could be determined accordingly to enable corresponding overload trainings with the centrifuge.Conclusion The proposed method facilitates the improvement of pilots'flight maneuvering performance in post stall super maneuvering flights under sustained high overload conditions.[Chinese Medical Equipment Journal,2025,46(7):21-26]

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Background and purpose:According to the latest data from the National Cancer Center,the incidence rate and mortality of lung cancer in China rank first among all malignant tumors,and 85%are non-small cell lung cancer(NSCLC).In recent years,immunotherapy based on programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)immune checkpoint inhibitors(ICIs)has made breakthrough progress in lung cancer,bringing more survival benefits to lung cancer patients.This study aimed to evaluate the cost-effectiveness of three major PD-L1 testing assays in guiding immunotherapy for patients with NSCLC,and to provide empirical evidence to guide the selection of cost-effective diagnosis and ICIs monotherapy regimens for NSCLC patients in China.Methods:From a healthcare system perspective,a decision-tree model was constructed to simulate the cost and effectiveness(percentage of the patients who were successfully diagnosed and who were correctly prescribed and underwent correct treatment according to China treatment guidelines)of employing Ventana PD-L1 IHC(SP263)assay,PD-L1 IHC 22C3 pharmDx,and Dako 22C3 antibody concentrate in early to mid-stage and advanced NSCLC patients in China,respectively.The cost-effectiveness of SP263 assay compared to other testing methods was assessed through the incremental analysis.The robustness of the base case analysis results was validated by using one-way sensitivity analysis and probabilistic sensitivity analysis.Results:When considering atezolizumab monotherapy following chemotherapy for early to mid-stage(Ⅱ A-Ⅲ B)NSCLC patients,in comparison to the 22C3 assay or 22C3 antibody concentrate,the SP263 assay incurred an additional cost of 9 449 yuan per successfully diagnosed and treated patient.The SP263 assay,which can guide multiple ICIs monotherapies(e.g.,atezolizumab,pembrolizumab)for advanced(Ⅳ)NSCLC patients,was dominant by achieving a higher percentage of successfully diagnosed and treated patients at a lower cost compared to Dako 22C3 assay and Dako 22C3 antibody concentrate.One-way sensitivity analysis and probabilistic sensitivity analysis both confirmed the robustness of the results.Conclusion:The Ventana PD-L1 IHC SP263 assay was cost-effective,compared to Dako PD-L1 IHC 22C3 assay and Dako 22C3 antibody concentrate for the immunotherapy treatment for both stage Ⅱ A-Ⅲ B and stage Ⅳ NSCLC patients in China.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.