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.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To construct a medical consumables selection indicator system based on analytic hierarchy process(AHP)and fuzzy cluster method.Methods Firstly,a medical consumables selection indicator system was established preliminarily with the literature research results and actual situation of hospital consumables management;secondly,13 experts in related fields were selected to execute two rounds of online questionnaires,the expert weights were determined with AHP,the importance of each selection indicator was scored by the expert evaluation method and fuzzy cluster method,and consistency analysis was carried out on the two rounds of expert evaluation results;finally,the final medical consumables selection indicator system was built with the 100-point scale.Results The constructed medical consumables selection indicator system was composed of 5 primary indicators,12 secondary indicators and 38 tertiary indicators.The primary indicators included consumables quality,clinical demand,cost-effectiveness,supply capacity and after-sales service,with the percentage-based scores being 27,25,14,26 and 8,respectively.Conclusion The medical consumables selection indicator system based on AHP and fuzzy cluster method with high reliability provides effective and reliable references for medical institutions to select medical consumables.

Objective To develop a novel protective ventilator circuit component and to verify its performance by water seal and anti-splash experiments.Methods A novel protective ventilator circuit component had a design scheme with the multifunctional joint,and consisted of a tee connection tube,an isolation sleeve and a stop sleeve,of which,the tee connection tube was made of polyethylene polymer material and the others were made of silicone material.The tee connection tube had a T-shaped structure with two standard connection ports,which was composed of an adapter,a sealing cap,a plug and a sealing ring;the isolation sleeve was in the shape of a cylinder with a raised bottom,which was inserted into the adapter;the stop sleeve was located in the isolation sleeve,with an inverted frustum of a cone at the bottom and a rounded hole in the middle of the inverted frustum.An open ventilator circuit tube was involved in the performance verification of the circuit component developed.In the water seal experiment,sputum aspiration was simulated and the heights of the liquid level drop in the L-shaped tubes were compared after sputum aspiration.In the anti-splash experiment,the infection rates on the surfaces of the sterile hole towels and gloves were calculated.Results Water seal experiment showed after sputum aspiration the open ventilator circuit tube had the liquid level at the L-shaped tube higher significantly than that of the circuit component;the anti-splash experiment indicated sputum aspiration resulted in the occurance of the splashing out of the secretion and 77.5%infection rate by the open ventilator circuit tube,while no splashing out and 0%infection rate by the circuit component developed.Conclusion The novel protective ventilator circuit component behaves well in sealing and anti-splashing,and thus is worthy of clinical application for sputum aspiration.[Chinese Medical Equipment Journal,2025,46(4):113-117]

Objective To construct a medical consumables selection indicator system based on analytic hierarchy process(AHP)and fuzzy cluster method.Methods Firstly,a medical consumables selection indicator system was established preliminarily with the literature research results and actual situation of hospital consumables management;secondly,13 experts in related fields were selected to execute two rounds of online questionnaires,the expert weights were determined with AHP,the importance of each selection indicator was scored by the expert evaluation method and fuzzy cluster method,and consistency analysis was carried out on the two rounds of expert evaluation results;finally,the final medical consumables selection indicator system was built with the 100-point scale.Results The constructed medical consumables selection indicator system was composed of 5 primary indicators,12 secondary indicators and 38 tertiary indicators.The primary indicators included consumables quality,clinical demand,cost-effectiveness,supply capacity and after-sales service,with the percentage-based scores being 27,25,14,26 and 8,respectively.Conclusion The medical consumables selection indicator system based on AHP and fuzzy cluster method with high reliability provides effective and reliable references for medical institutions to select medical consumables.

Objective:This study implemented a pulmonary rehabilitation integrated care management model based on an Internet of things platform for patients with chronic obstructive pulmonary disease (COPD) and evaluated its effectiveness to provide evidence for clinical respiratory rehabilitation practices.Methods:A quasi-experimental design was adopted. Patients from the Department of Respiratory and Critical Care Medicine at Changsha Central Hospital Affiliated to University of South China between May and December 2023 were selected via purposive sampling. Sixty COPD patients from May to August 2023 were assigned to the control group, while 60 patients from September to December 2023 were assigned to the comprehensive management group. The control group adopted routine respiratory rehabilitation management, the comprehensive management group adopted a pulmonary rehabilitation integarted care management mode based on Internet of things platform respiratory rehabilitation. Before and after 6 months of intervention, patients were assessed for respiratory rehabilitation compliance, lung function (including the percentage of forced expiratory volume in the first second to the expected value (FEV 1% pred) and the ratio of forced expiratory volume in the first second to forced vital capacity (FEV 1/FVC), 6-minute walk test (6MWT) and COPD Assessment Test (CAT). Results:Finally, 55 cases were included in the control group and 59 cases were included in the comprehensive management group. The control group included 32 males and 23 females, aged (67.31 ± 7.14) years. The comprehensive management group included 39 males and 20 females, aged (68.15 ± 6.34) years. The respiratory rehabilitation compliance score, FEV 1% pred, FEV 1/FVC, 6MWT, and CAT score of the full management group after intervention were as follows: (26.45 ± 1.51) points, (59.21 ± 6.68)%, (78.35 ± 8.01)%, (479.63 ± 54.70) m, and (12.35 ± 4.01) points, which were all better than the control group′s (15.68 ± 1.56) points, (44.09 ± 6.31)%, (68.38 ± 6.43)%, (429.82 ± 60.50) m, and (17.03 ± 4.23) points. The difference between two groups were significant ( t values were 1.83-5.24, all P<0.05). Conclusions:The pulmonary rehabilitation integarted care management model based on Internet of things platform improves patient compliance, enhances pulmonary function, enhance their activity endurance, and improve their quality of life. It is worth promoting and using in clinical practice.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Objective To develop a novel protective ventilator circuit component and to verify its performance by water seal and anti-splash experiments.Methods A novel protective ventilator circuit component had a design scheme with the multifunctional joint,and consisted of a tee connection tube,an isolation sleeve and a stop sleeve,of which,the tee connection tube was made of polyethylene polymer material and the others were made of silicone material.The tee connection tube had a T-shaped structure with two standard connection ports,which was composed of an adapter,a sealing cap,a plug and a sealing ring;the isolation sleeve was in the shape of a cylinder with a raised bottom,which was inserted into the adapter;the stop sleeve was located in the isolation sleeve,with an inverted frustum of a cone at the bottom and a rounded hole in the middle of the inverted frustum.An open ventilator circuit tube was involved in the performance verification of the circuit component developed.In the water seal experiment,sputum aspiration was simulated and the heights of the liquid level drop in the L-shaped tubes were compared after sputum aspiration.In the anti-splash experiment,the infection rates on the surfaces of the sterile hole towels and gloves were calculated.Results Water seal experiment showed after sputum aspiration the open ventilator circuit tube had the liquid level at the L-shaped tube higher significantly than that of the circuit component;the anti-splash experiment indicated sputum aspiration resulted in the occurance of the splashing out of the secretion and 77.5%infection rate by the open ventilator circuit tube,while no splashing out and 0%infection rate by the circuit component developed.Conclusion The novel protective ventilator circuit component behaves well in sealing and anti-splashing,and thus is worthy of clinical application for sputum aspiration.[Chinese Medical Equipment Journal,2025,46(4):113-117]

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 investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.