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.

Gastric cancer remains a highly prevalent malignancy worldwide, with surgical resection currently constituting the cornerstone of treatment aimed at improving long-term patient survival. Owing to their notable advantages, including reduced surgical trauma and accelerated postoperative recovery, minimally invasive procedures are progressively supplanting conventional open surgery and have become the mainstream approach in gastric cancer management. Concurrently, the rapid advancement of artificial intelligence (AI) technologies has enabled real-time intraoperative monitoring of surgical scenes, thereby furnishing novel technical support for adjunctive decision-making, surgical navigation, and skill assessment during gastrectomy. This article provides a systematic review of the current status of AI applications in minimally invasive gastric cancer surgery, with a particular focus on research progress pertaining to instrument recognition, surgical phase identification, delineation of normal anatomical structures, detection of metastatic foci, and early warning of intraoperative adverse events. Furthermore, we discuss the potential value of AI in enhancing surgical efficiency, ensuring patient safety, and optimizing surgical education. On this basis, we further analyze the principal challenges and inherent risks confronting current AI systems, with the aim of informing future technological innovation and facilitating clinical translation.

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.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Asthe standard for drafting standards,the Rules for Compiling National Standards for Pharmaceutical Excipients was first issued in the 2020 edition and then revised and re-issued in 2025.It has become an important technical specification for the pharmaceutical excipients standards in the Chinese Pharmacopoeia and for the phar-maceutical excipients standards formulated by pharmaceutical companies for associated review and approval.This article focuses on introducing the working background,main framework and main characteristics of the Rules for Compiling National Standards for Pharmaceutical Excipients,aiming to help the drafters,reviewers and implement-ers of pharmaceutical excipients standards better understand and master them,so as to further improve the standard-ization of writing pharmaceutical excipients standards and enhance the level of standards formulation and revision of pharmaceutical excipients.

Objective To explore the correlation between serum homocysteine(Hcy),25-hydroxyvitamin D[25(OH)D]and frailty with type 2 diabites mellitus(T2DM)complicated with sarcopenia.Methods From September 2021 to March 2023,210 elderly T2DM patients were selected from the Department of Geriatrics of The First People's Hospital of Yunnan Province,and divided into simple T2DM(n=99)group,mild sarcopenia(M-Sar,n=59)group and severe sarcopenia(S-Sar,n=52)group.The"Elderly Comprehensive Assessment System"was used to evaluate subjects.The influencing factors of T2DM complicated with sarcopenia were analyzed by Logistic regression.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of Hcy,25(OH)D combined with frailty in evaluating T2DM with sarcopenia.Results In T2DM,M-Sar and S-Sar groups,the age,Hcy,the risk rate of balance gait work falling and the rate of weakness increased in turn(P<0.05),while BMI,hemoglobin,25(OH)D,the rate of good nutrition,the normal rate of basic daily living,the low risk rate of falling,the rate of good balance gait function and the rate of no weakness decreased in turn(P<0.05).Logistic regression analysis showed that serum Hcy,frailty and 25(OH)D were the influencing factors of senile T2DM complicated with sarcopenia.Hcy,25(OH)D and frailty combined to predict T2DM with sarcopenia had an area under ROC carve of 0.815,with a sensitivity of 0.811 and a specificity of 0.717.Conclusions Serum Hcy,25(OH)D and frailty are closely related to T2DM combined with sarcopenia.Detection of Hcy and 25(OH)D combined with frailty score is helpful for early diagnosis of sarcopenia in primary hospitals.

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition,the Chinese Pharmacopoeia 2025 has been completed.Among them,52 new pharmaceutical excipients monographs have been added,and the total number has reached 387.245 pharmaceutical excipients monographs have been revised,of which 109 monographs have only textual revisions and 136 monographs have substantive revi-sions.This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025,which can contribute to accurately understand and utilize the stand-ards in Chinese Pharmacopoeia.

Objective:To evaluate the therapeutic efficacy of combined therapy with a speaking valve and transcranial direct current stimulation (tDCS) for dysphagia in stroke patients post-tracheostomy.Methods:This retrospective case-control study enrolled 120 stroke patients with post-stroke tracheostomy-associated dysphagia, admitted to the Department of Rehabilitation Medicine at Huai′an Second People′s Hospital. Participants were randomly allocated to either a control group [45 males and 15 females, aged from 46 to 78 (65.78±8.68) years]receiving tDCS and conventional rehabilitation or an intervention group [41 males and 19 females, aged from 46 to 79 (66.32±9.18) years]receiving tDCS plus speaking valve therapy, with 60 patients per group. Swallowing function was assessed before and after a 3-week intervention using the Standardized Swallowing Assessment (SSA), Water Swallowing Test (WST) grading, Functional Oral Intake Scale (FOIS), and Swallowing-quality of life score (SWAL-QOL).The SPSS 22.0 was used for statistical analysis.Results:The intervention group demonstrated a significantly higher overall treatment response rate than the control group [95.0%(57/60) vs 78.3%(44/56), χ2=-6.056, P<0.001]. Post-treatment, the intervention group showed significantly greater improvements, as evidenced by a lower SSA score (21.50±1.82 vs 24.92±1.42, t=-11.480, P<0.001) and superior WST grades (observation group: 45 cases at grade 1, 12 cases at grade 2, 5 cases at grade 3; control group: 33 cases at grade 1, 11 cases at grade 2, 16 cases at grade 3, Z=5.484, P<0.001). Furthermore, the intervention group achieved significantly higher FOIS scores (observation group: 1 case at grade 1, 1 case at grade 2, 1 case at grade 4, 8 cases at grade 5, 7 cases at grade 6, 45 cases at grade 7; control group: 2 cases at grade 1, 7 cases at grade 2, 3 cases at grade 3, 4 cases at grade 4, 5 cases at grade 5, 6 cases at grade 6, 33 cases at grade 7, Z=-3.559, P<0.001) and greater improvements in SWAL-QOL scores ( P<0.001), indicating enhanced oral intake and quality of life. Conclusion:The combination of a speaking valve and tDCS effectively promotes the swallowing recovery and improves quality of life in stroke patients with post-tracheostomy dysphagia. This combined modality represents a promising and effective therapeutic strategy for this patient population.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*