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.

Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective:To evaluate the efficacy and safety of anlotinib neoadjuvant therapy for newly diagnosed locally advanced thyroid cancer (LATC).Methods:Twenty-four newly diagnosed LATC patients (10 males and 14 females, age (47.1±3.3) years) admitted to Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine were prospectively included from January 2023 to April 2024. Patients were given anlotinib neoadjuvant therapy (12mg/d, 2 weeks of medication, 1 week of discontinuation), and the efficacy of the treatment was evaluated by CT and multi-disciplinary treatment at the end of each treatment cycle. Patients assessed as suitable for surgery would be scheduled for surgery, while those who were not suitable for surgery would continue to receive neoadjuvant therapy and periodic evaluations. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the R0/1 resection rate and adverse events (AE) after neoadjuvant therapy were observed. Paired- t test was used to analyze the differences between groups, and the Clopper-Person accurate method was used to calculate the bilateral 95% CI of ORR and other indicators. Results:Twenty-four patients received 2(2, 3) cycles of neoadjuvant therapy with anlotinib, of which 23 underwent surgery after anlotinib therapy. After neoadjuvant therapy, the mean maximum diameter of target lesions decreased by 23.5%(95% CI: 2.8%-44.3%) compared with baseline ( t=9.22, P<0.001). The ORR and DCR were 37.5%(95% CI: 18.8%-59.4%) and 100%(95% CI: 85.8%-100%), respectively. About 91.7%(95% CI: 73.0%-99.0%) of patients eventually underwent R0/1 resection. Hand and foot skin reactions, hypertension, oral mucositis, and leukopenia were common AE; grade 4 and 5 AE were not observed. Conclusion:Anlotinib can be safely used as neoadjuvant therapy for newly diagnosed LATC patients with good antitumor effects, providing better surgical opportunities for R0/1 resection.

Under the guidance of five-viscus correlation theory,and with reference to the clinical practice,this paper discusses the pathogenesis of cardiogenic asthma,i.e.long illness of the heart resulting in asthma,from the perspective of physiological characteristics of heart,which belongs to yin in essence and yang in function.And this paper also introduces the correlation between five zang-organs and cardiogenic asthma:asthma induced by heart failure involves the lung,has close relation with middle energizer(spleen and stomach),results from the comorbidity of heart and liver,and contributes to the disorders of kidney.It is believed that cardiogenic asthma injures the heart,results in internal blockage of blood stasis,so the original pathogenesis of cardiogenic asthma is due to the heart;unsmoothed blood circulation causes fluid retention in the chest and lung,and then the lung is involved.The failure of spleen and stomach in generation and transportation will cause the unsmoothed circulation of qi and blood,liver qi stagnation will result in the failure of liver blood in nourishment,and the intense kidney yin-fire will stir upward and attack heart yang.The factors mentioned above all are prone to result in the aggravation of cardiogenic asthma.Therefore,the treatment of cardiogenic asthma with traditional Chinese medicine should be focused on heart,and methods of replenishing qi,activating blood circulation,and inducing diuresis are used as the primary therapeutic approaches.Moreover,according to the organs involved in cardiogenic asthma,therapies of regulating the five viscera and restoring the balance of yin and yang are used for precise treatment,and the therapeutic effect will be enhanced.

Objective To design a night vision simulation training system to provide pilots with practical training on ground night vision goggles.Methods The system had its hardware composed of a control stick,a throttle lever,rudder pedals,a head-up display(HUD),a control box,a computer,a projector and a screen.The HUD and control box were designed using night vision-compatible lighting technology to simulate the ambient light conditions pilots experienced when flying with night vision goggles.The software of the system consisted of five ones developed with C++programming languge for visual scene simulation,instrument simulation,flight performance simulation,integrated management control and cockpit manage-ment.Night vision images and computer-rendered images of typical scenes with varying brightness levels were collected.Objective image evaluation metrics such as contrast and brightness were used as inputs,while subjective evaluation data served as outputs to construct and train a support vector machine(SVM)model.Totally 30 typical night vision training scenarios were selected based on model validation and optimization to evaluate the system's optical fidelity.Results The average fidelity score for the 30 typical night vision training scenarios was 8.05,indicating that the system could realistically simulate terrain and landscapes under various lighting and weather conditions during night flights and static and dynamic targets in the air,on the ground and at sea.Conclusion The system meets the desired requirements and effectively facilitates night vision training for pilots.[Chinese Medical Equipment Journal,2025,46(3):21-26]

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P＜0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR＞1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.

Three typical failures of large-aperture 16-slice spiral Siemens SOMATOM Sensation Open CT were introduced in terms of phenomenon,cause and treatment method.References were provided for medical engineers to treat similar failures.