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:Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome,but the specific mechanism is not yet clear.OBJECTIVE:To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.METHODS:A total of 70 SD rats were randomly divided into a normal control group(n=10),a model group(n=15),a western medicine group(n=15),a low-dose Huosui Formula group(n=15),and a high-dose Huosui Formula group(n=15).Except for the normal control group,the other four groups were injected with dimethyl benzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models.After modeling,the normal control group and the model group were given normal saline;the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg,and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula,respectively,by intragastric administration once a day for 28 consecutive days.Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation.Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.RESULTS AND CONCLUSION:(1)Compared with the normal control group,peripheral blood leukocyte,neutrophil,hemoglobin,platelet,and CD4+,CD4+/CD8+levels were decreased in the model group significantly(P＜0.05),while CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+expressions were significantly upregulated(P＜0.05).(2)In all dosage groups,myelopoietic proliferation was increased compared with the model group,with no significant difference between the groups(P＞0.05).(3)Compared with the model group,leukocytes,hemoglobin,platelets,and CD4+,CD4+/CD8+were significantly elevated in the high-dose Huosui Formula group(P＜0.05),the expression of CD8+was significantly lower(P＜0.05),and the levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+were down-regulated but not statistically significant(P＞0.05).(4)The western medicine group and the high-dose Huosui Formula group showed similar efficacy.The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group.These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats,increase the levels of CD4+,and CD4+/CD8+while down-regulate the expression levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+.These observations suggest a link to the negative immunoregulation mechanism.

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.

BACKGROUND:Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome,but the specific mechanism is not yet clear.OBJECTIVE:To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.METHODS:A total of 70 SD rats were randomly divided into a normal control group(n=10),a model group(n=15),a western medicine group(n=15),a low-dose Huosui Formula group(n=15),and a high-dose Huosui Formula group(n=15).Except for the normal control group,the other four groups were injected with dimethyl benzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models.After modeling,the normal control group and the model group were given normal saline;the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg,and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula,respectively,by intragastric administration once a day for 28 consecutive days.Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation.Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.RESULTS AND CONCLUSION:(1)Compared with the normal control group,peripheral blood leukocyte,neutrophil,hemoglobin,platelet,and CD4+,CD4+/CD8+levels were decreased in the model group significantly(P＜0.05),while CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+expressions were significantly upregulated(P＜0.05).(2)In all dosage groups,myelopoietic proliferation was increased compared with the model group,with no significant difference between the groups(P＞0.05).(3)Compared with the model group,leukocytes,hemoglobin,platelets,and CD4+,CD4+/CD8+were significantly elevated in the high-dose Huosui Formula group(P＜0.05),the expression of CD8+was significantly lower(P＜0.05),and the levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+were down-regulated but not statistically significant(P＞0.05).(4)The western medicine group and the high-dose Huosui Formula group showed similar efficacy.The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group.These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats,increase the levels of CD4+,and CD4+/CD8+while down-regulate the expression levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+.These observations suggest a link to the negative immunoregulation mechanism.

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 investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

A total of 18 batches of Zhuru Decoction samples were prepared. Chromatographic fingerprints were established for Zhuru Decoction and single decoction pieces, the content of which was then determined. The extraction rate ranges, content, and transfer rate ranges of puerarin, liquiritin, and glycyrrhizic acid, together with the common peaks and the similarity range of the fingerprints, were determined to clarify key quality attributes of Zhuru Decoction. The 18 batches of Zhuru Decoction samples had 25 common peaks and the fingerprint similarity higher than 0.95. Puerariae Lobatae Radix, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens had 21, 3, and 1 characteristic peaks, respectively. The 18 batches of samples showed the extraction rates within the range of 18.45%-25.29%. Puerarin had the content of 2.20%-3.07% and the transfer rate of 38.5%-45.9%; liquiritin had the content of 0.24%-0.85% and the transfer rate of 15.9%-37.5%; glycyrrhizic acid had the content of 0.39%-1.87% and the transfer rate of 16.2%-32.8%. In this paper, the quality value transmitting of substance benchmarks of Zhuru Decoction was analyzed based on chromatographic fingerprints, extraction rate, and the content of index components. A scientific and stable method was preliminarily established, which provided a scientific basis for the quality control and formulation development of Zhuru Decoction.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Glycyrrhizic Acid/analysis* ; Quality Control ; Rhizome/chemistry*