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.

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: The phase 2, open-label, randomized, 3-arm study (NCT03776812) found that intermittently dosed relacorilant + nab-paclitaxel improved progression-free survival, duration of response, and overall survival compared with nab-paclitaxel monotherapy with minimal additional toxicity. This study analyzed the cost-effectiveness of intermittent relacorilant + nab-paclitaxel (IN), continuous relacorilant + nab-paclitaxel (CN) and nabpaclitaxel monotherapy (N) from the payer’s perspective over a 5-year time horizon. Methods: The health outcome is expressed in quality-adjusted life years (QALYs). IN, CN and N were evaluated using QALYs and incremental cost-effectiveness ratio (ICER). The data for this model come from the NCT03776812 trial and other published literature. The impact of the variables is studied using a one-way deterministic sensitivity analysis and a probabilistic sensitivity analysis based on a second-order Monte Carlo simulation. Results: N was the least costly strategy, at $ 4606.05, followed by IN ($22,597.75) and CN ($44,276.86). Based on a willingness-to-pay threshold of $100,000/QALY, IN was costeffective compared with N, with an ICER of $21,418.69 per QALY gained for N, whereas CN was ruled out by extended dominance (less effective, more costly), compared with N. The incremental benefits of IN compared to CN and N were 0.72 QALYs and 0.84 QALYs. Conclusion From a US health care system perspective, IN may be cost-effective compared to CN for patients with recurrent platinum-resistant ovarian cancer, and IN is also better than CN and N in terms of efficacy. Therefore, IN is a high-quality regimen for clinicians to treat patients with recurrent platinum-resistant ovarian cancer.

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 explore the impact of different preoperative fluid supplementation methods (oral multidimensional carbohydrates and conventional fluid supplementation) on early postoperative recovery and pain management in patients undergoing unilateral biportal endoscopic (UBE) spine surgery.Methods:A retrospective cohort study was conducted to analyze the data of 386 patients who underwent UBE lumbar spine surgery under general anesthesia in the two courtyards of Beijing Friendship Hospital Affiliated to Capital Medical University from May 2023 to April 2024. All patients were divided into oral multidimensional carbohydrates ( "Outfast" supplementation, composed mainly of water, sugars, salts, and vitamins) group (referred to as oral "Outfast" group, 189 patients) and conventional fluid supplementation group (197 patients) according to the type of fluid replenishment. Patients in the oral "Outfast" group were given one oral dose in the morning of the first surgery, and another oral infusion before 10∶00 in the morning of the next surgery or afternoon surgery. Patients in the conventional fluid supplementation group received intravenous infusion in the morning of the first surgery, and were given intravenous infusion of glucose and sodium chloride injection in the morning of the next surgery or afternoon surgery. The two groups were compared for the proportion of patients receiving preoperative intravenous fluids on the day of surgery, intraoperative and postoperative fluid volumes, average daily fluid volumes over the first three postoperative days, time to first postoperative ambulation, time to first bowel movement, post-anesthesia care unit (PACU) stay duration, 4-hour and 24-hour postoperative visual analog scale (VAS) pain scores, incidence of anesthesia-related adverse reactions, and incidence of severe gastrointestinal adverse reactions. The measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. The measurement data of skewed distribution were expressed as M ( Q1, Q3) and rank sum test was used for inter-group comparison. Count data was presented in terms of examples and percentages, and a chi-square test was used for comparison between two groups. Results:In the oral "Outfast" group, 8 patients (4.2%) received preoperative intravenous fluids on the day of surgery, compared to 136 patients (69.0%) in the conventional fluid supplementation group, showing a significant difference ( P<0.001). The postoperative fluid volumes, average daily fluid volumes over the first three postoperative days, and shorter time to first ambulation in the oral multidimensional carbohydrates group were 700.0(600.0, 1 100.0) mL, 200.0(200.0, 300.0) mL, and 6.0(6.0, 11.0) h, respectively. The conventional fluid supplementation group was 1 100.0(700.0, 1 200.0) mL, 600.0(500.0, 700.0) mL, and 12.0(6.0, 19.0) h, respectively. The oral "Outfast" group was lower than the conventional fluid supplementation group ( P<0.001).There were no significant differences between the two groups in intraoperative fluid volumes, time to first bowel movement, PACU stay duration, 4-hour and 24-hour VAS pain scores, incidence of anesthesia-related adverse reactions, or incidence of severe gastrointestinal adverse reactions ( P>0.05). Conclusions:Preoperative oral multidimensional carbohydrates supplementation effectively reduces the amount of preoperative and postoperative intravenous fluid required, shortens the time to first ambulation. Preoperative oral multidimensional carbohydrates is safe and does not adversely impact gastrointestinal reactions or pain management in the postoperative period.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

In the past few decades,supercritical fluid chromatography(SFC)as a supplement to liquid chromatography(LC)separation technology has attracted people's interest,especially in the combination of SFC and mass spectrometry(MS),which has shown important application prospects in metabolomics,lipidomics,and other fields.Compared to the interface of LC-MS,the interface of SFC-MS presents some unique challenges that require special solutions to be designed.This article categorizes and summarizes the existing interfaces used for SFC-MS,focuses on the impact of different interface designs on detection performance,provides the applicable characteristics of different types of interfaces,and finally briefly introduces the application progress of SFC-MS in different fields.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective To analyze the incidence rate of birth defects in infants born at different gesta-tional ages and birth weights,so as to provide a basis for improving the surveillance system and reducing the inci-dence of birth defects.Methods Data of all perinatal infants born at and after 28 weeks of gestation and within 7 days after delivery in all the hospitals with the obstetrical department from October 1,2003 to September 30,2015 were collected.Results From 2003 to 2015,1 236 937 perinatal infants were monitored,including 10 619 with birth defects(incidence rate of 8.59‰).Among the infants with birth defects identified by the hos-pital surveillance system of birth defects in Xi'an during the study period,3 306,3 473,and 224 infants showed the birth weights less than 2 500 g,the gestational age within the range of[28,37]weeks,and the gestation age≥42 weeks,respectively.The low birth weight infants showed higher incidence rate of birth defects than the normal birth weight infants(χ2 =37 097.79,P<0.001).The premature infants(gestational age<37 weeks)and postterm infants(gestational age≥42 weeks)showed higher incidence rates of birth defects than in-fants born at normal gestational age(χ2 =24 998.24,P<0.001;χ2 =196.40,P<0.001).The top five birth defects of low birth weight infants were congenital hydrocephalus,spina bifida,congenital heart disease,anen-cephaly,and cleft lip and cleft palate.The outcomes of birth defects in normal weight infants and low weight in-fants were mainly live births(68.60%)and stillbirths(54.72%),respectively,which showed a significant difference(χ2 =647.59,P<0.001).The main outcomes of birth defects in the infants born at normal gestation age,postterm infants,and premature infants were mainly live births(77.38%),live births(83.93%),and stillbirths(57.79%),respectively,which showed significant differences(premature infants vs.infants born at normal gestation age:χ2 =2 025.08,P<0.001;premature infants vs.postterm infants:χ2 =245.39,P<0.001;infants born at normal gestation age vs.postterm infants:χ2 =16.28,P =0.001).Conclusions Pre-mature infants,low birth weight infants,and postterm infants showed significantly higher incidence rate of birth defects than the infants born at normal gestation age.The outcomes of birth defects had significant differences be-tween low birth weight infants and normal birth weight infants,between premature infants and infants born at nor-mal gestation age,between premature infants and postterm infants,and between infants born at normal gestation age and postterm infants.