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.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.

Biochemistry,as a fundamental course for science and engineering majors related to biology and chemistry,holds a significant position in the curriculum.The course team at Dalian Minzu University is committed to teaching innovation,adopting the outcome-based education(OBE)concept for teaching de-sign and incorporating ideological and political elements,in order to achieve the dual goals of knowledge transmission and value guidance.The team has established a three-dimensional teaching goal of"knowl-edge,morality,and ability",covering"consolidating core knowledge,cultivating moral sentiment,and enhancing innovation ability".Through a multi-dimensional integrated teaching method of"three integra-tions and five combinations",multiple rounds of teaching practice have been carried out in the applied chemistry major using"classification and specificity of enzyme"as an example.The output of teaching re-sults and survey questionnaires show that students highly recognize the teaching design and its"process-based learning"evaluation method,fully reflecting the student-centered teaching idea.Research has shown that OBE design combined with ideological and political elements can effectively promote students' knowl-edge acquisition,moral growth,and innovation ability improvement in the course of Biochemistry.This teaching design not only helps students construct correct worldviews,outlooks on life,and values,but also significantly enhances their innovative thinking and practical abilities.This teaching design can not only ef-fectively improve the teaching quality of the course,but also provide new perspectives and ideas for the teaching design of Biochemistry,realizing the organic integration of professional knowledge imparting and i-deological and political education,and has certain innovation and practical significance.

Objective To design a new type of elastic gloves for burn scar rehabilitation to solve the problems of conventional elastic gloves in pressure distribution,elasticity maintenance and absorption of sweat stains.Methods The new elastic gloves was made of non-woven fabric by spandex material,which was composed of external and internal parts.The main body of the external part was used as the primary structure of the gloves,which was provided with a sealing strip,a storage bag,a drawstring,etc.The internal part consisted of a bonding sheet,an elastic band,a fiber sheet,an absorbent sponge,some breathable holes,etc.Results The new elastic gloves designed could be used for the pressure therapy for the scars on the opisthenar,palm side,finger web and purlicue with scar proliferation inhibitted effectively,and the breathable hole and absorbent sponge contributed to the absorption of the sweat of the patient.Conclusion The new type of elastic gloves gains advantages in elasticity,wearing comfort and effectiveness of the pressure therapy for purlicue and finger web,and can be used for the pressure therapy to inhibit proliferative scarring after burns.[Chinese Medical Equipment Journal,2025,46(8):118-120]

Aim To investigate the effect of total gly-cosides of peony on Th17/Treg balance in autoimmune thyroiditis(AIT)by regulating miR-155 expression.Methods Sixty female SD rats were randomly divided into a blank control group,a model group,high-dose,medium,and low-dose groups of total glycosides of peony,and a Western medicine control group(seleni-um yeast group).After eight weeks of modeling,the pathological changes in thyroid tissue were observed by HE staining,the expression of miR-155 in the thyroid of rats was detected by RT-PCR,the targeting effect of miR-155 on SOCS1 was verified by dual luciferase method,and the levels of TGAb,TPOAb,IL-10,and IL-17 in peripheral serum were detected by ELISA,the expression of thyroid SOCS1 was detected by WB,and the proportion of Th17 and Treg in CD4+cells of the spleen was detected by flow cytometry.Results Com-pared with the blank group,the expression of miR-155 in the thyroid gland of the model group rats significant-ly increased,and the serum levels of TGAb,TPOAb,and IL-17 significantly increased,with an increase in the proportion of Th17;the IL-10 level significantly decreased,the proportion of Treg decreased,and the expression of SOCS1 protein decreased,with statistical significance(P＜0.01);compared with the model group,the high,medium,and low dose groups of total glycosides of peony and selenium yeast groups showed a decrease in miR-155 expression,a decrease in TGAb,TPOAb,IL-17 levels,a decrease in Th17 pro-portion,an increase in IL-10 level,an increase in Treg proportion,and an increase in SOCS1 expression,all with statistical significance(P＜0.01).Moreover,the improvement in the medium dose group of total glyco-sides of peony was more significant.Conclusion To-tal glycosides of peony downregulate miR-155 expres-sion,regulate Th17/Treg balance,alleviate inflamma-tory response,and exert immune regulatory effects.

Objective:To prepare nanoscale docetaxel-loaded lipid microbubbles(DLLM),characterize their physical and chemical properties,evaluate their biosafety and anti-tumor effects in vitro,and explore their potential as a targeted delivery system for chemotherapeutic drugs.Methods:DLLM was prepared by thin film hydration method.The morphology,particle size and distribution were characterized by transmission electron microscopy,scanning electron microscopy and particle size analyzer.The drug encapsulation efficiency was determined by high performance liquid chromatography.Human hepatoma HepG2 cells were used as a model to set up the control group(Control group),the docetaxel group(DOC group),the docetaxel-loaded lipid microbubbles group(DLLM group)and the docetaxel-loaded lipid microbubbles+ultrasound group(DLLM+US group).The cell morphology was observed by optical microscope,the cell survival rate was detected by CCK-8 method,and the apoptosis was detected by flow cytometry.The biocompatibility of microbubbles and their mediated ultrasound-enhanced anti-tumor effect were evaluated.Results:The prepared DLLM was regular spherical,with a particle size distribution range of 200-600 nm,an average particle size of 380 nm,and an encapsulation efficiency of 80.3％±2.6％.The cell viability of the DOC group and the DLLM+US group was significantly lower than that of the Control group(P＜0.01),and the apoptosis rate was significantly increased(P＜0.01).The cell viability of the DLLM+US group was lower than that of the DOC group(P＜0.05),and the apoptosis rate was higher than that of the DOC group(P＜0.05).There was no significant difference in cell viability and apoptosis rate between the DLLM group and the Control group(P＞0.05).Conclusions:The nano-scale DLLM prepared in this experiment has uniform particle size,high encapsulation efficiency,good stability and biocompatibility.DLLM can enhance the killing and pro-apoptotic effects of docetaxel on HepG2 cells under ultrasound irradiation.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To propose a preventive maintenance strategy of the heating,ventilation and air-conditioning(HVAC)system in pharmacy intravenous admixture services(PIVAS)based on the reliability centered maintenance(RCM)method so as to provide references for PIVAS equipment maintenance.Methods Firstly,a HVAC system RCM review team was formed,and the failure modes and impacts of important functional components of the equipment were analyzed to clarify the consequences of the failure of each functional component under the premise of ensuring the safety and integrity of the equipment and with the goal of minimizing the loss of maintenance downtime and the consumption of maintenance resources.Secondly,with a standardized logical decision-making procedure the preventive maintenance strategy was determined and implemented based on the consequences of functional failure.Finally,statistical analyses were carried out on such equipment indicators as performance parameter qualification rate,failure rate and maintenance cost before and after the RCM method-based strategy was executed,in order to evaluate the efficacy of the strategy.Results The RCM method-based preventive maintenance strategy had the performance qualification rate increased from 97.47%to 99.06%(χ2=24.139,P<0.01),the failure rate decreased from 0.24%to 0.03%(χ2=13.519,P<0.01)and the maintenance cost reduced by 11.5%,from RMB 134,200 to 118,700.Conclusion The RCM method-based preventive maintenance strategy provides reliable equipment for PIVAS and lowers the maintenance cost effectively,and references are given for the development of automated and intelligent equipment maintenance strategies for PIVAS.[Chinese Medical Equipment Journal,2025,46(10):78-83]