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.

The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

Objective: This study examined the status and effectiveness of the “Emergency Imaging Interpretation Support Project in Vulnerable Areas,” which was implemented to provide rapid treatment and improve the service quality for patients in vulnerable areas with inadequate emergency medical infrastructure. After evaluating the project effectiveness, this paper discusses future development directions. Methods: This study was retrospective. The categorical variables were analyzed using frequency tables and chi-square tests, while the continuous variables were presented as means. Analysis of variance was used to compare the satisfaction survey results across the 3 years. Results: Compared with patients in nonvulnerable areas, patients in vulnerable areas were more likely to visit local emergency medical facilities (P<0.001), had a higher proportion of Korean Triage Acuity Scale levels 4 and 5 (P<0.001), and were also significantly older (P<0.001). Satisfaction with the reduction in time required to provide definitive treatment was highest in 2023 (P=0.005), but satisfaction with all other survey items was highest in 2024. Conclusion The project to support imaging interpretation in vulnerable areas will greatly help provide rapid treatment to emergency patients in vulnerable areas. Nevertheless, policies and measures are needed to encourage their participation because few institutions have participated in the project.

Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To evaluate the application effect of improved problem-based learning (PBL) based on 5W2H thinking in the course of "massage therapy".Methods:The undergraduate students in Class 1 and Class 2 of Acupuncture and Massage in the first semester of the 2023-2024 academic year at Heilongjiang University of Chinese Medicine were selected as the research subjects. The "massage therapy" was taught in Class 1 with the traditional method (control group, n=66) and in Class 2 with the method of improved PBL with 5W2H thinking (observation group, n=68). The two groups of students were compared in terms of theoretical knowledge of massage therapy, the assessment of massage skills, comprehensive ability, innovation ability, and practical ability, as well as the procedural evaluation indicators of massage. SPSS 25.0 was used for normality test and t test χ2 test. Results:After the completion of the study, the observation group showed higher scores in theoretical knowledge (90.56±11.73), massage skill proficiency [(87.22±11.57) vs. (78.23±9.45)], massage skill demonstration [(84.56±11.20) vs. (74.69±9.13)], mannequin usage [(82.98±10.75) vs. (72.66±8.89)], and massage skill mechanics [(86.38±11.45) vs. (73.35±8.94)] compared to the control group. The observation group also outperformed the control group in medical humanities [(85.53±10.64) vs. (64.86±7.33)], teacher-student and student-student interaction [(85.35±8.67) vs. (80.15±7.46)], clinical thinking and operation [(90.05±12.13) vs. (74.26±8.94)], and team coordination and cooperation [(85.60±10.06) vs. (81.53±9.33)]. In addition, the observation group scored higher than the control group in learning participation rate [(18.20±3.75) vs. (13.15±2.93)], error correction rate [(27.56±5.85) vs. (22.11±4.62)], operational stability [(48.43±7.79) vs. (42.06±6.60)], and total score [(94.19±7.56) vs. (77.32±6.78)].Conclusions:The application of improved PBL based on 5W2H thinking in the course of "massage therapy" has significant clinical implications. It can not only improve the teaching quality and effect, but also cultivate students' clinical thinking, teamwork, learning interest, and innovation ability, making it suitable for further promotion and application.

Objective To revise the Inventory of Alienation Toward Parents(IAP)and test its reliability and validity in a military population in order to provide a scientific tool for assessing the level and grade of parent-child alienation among military personnel.Methods Whole-cluster stratified random sampling was used to subject 8 641 service members from 8 Army units.Then all participants were surveyed with 18-item adolescent IAP,Beck Depression Inventory-Ⅱ,and Generalized Anxiety Disorder-7.SPSS 27.0 and AMOS 26.0 were used to perform item analysis,exploratory factor analysis(EFA),and confirmatory factor analysis(CFA)to assess reliability and validity.Subsequently,our revised 16-item version of IAP was employed to develop means,percentiles,cut-off scores,and category norms.Results ①Items 3 and 12 were deleted in item analysis.②EFA extracted the original communication and emotional distance factors;CFA indicated that the two-factor model had good fitness,with the mother-child alienation scale:χ2/df=4.248,comparative fit index(CFI)=0.962,Tucker-Lewis index(TLI)=0.929,root mean square error of approximation(RMSEA)=0.028,standardized root mean squared residual(SRMR)=0.023;while the father-child alienation scale:χ2/df=5.41,CFI=0.939,TLI=0.901,RMSEA=0.032,SRMR=0.044.③The internal consistency reliability of the total IAP was good(0.744～0.888).④The total IAP score and scores of the mother-child and father-child subscales were positively correlated with depression and anxiety(r=0.395～0.493,P<0.01).⑤ The average total IAP score for military personnel was 17.27±4.21,and the scores of mother-child alienation and father-child alienation were 8.64±2.26 and 8.62±2.43,respectively.With percentiles of P75 and P90 as the cut-off points,the total IAP score can be stratified into 3 levels,that is,normal(≤16),moderate(17～19),and severe(≥20).Then,additional category norms were developed based on demographic characteristics.Conclusion Our revised 16-item military version of IAP shows good reliability and validity.A preliminary and representative norm is developed primarily,and can be used to assess the level and grade of military parental alienation.

Background: Psychological test reports are essential in assessing intellectual functioning, aiding in diagnosing and treating intellectual disability (ID) and attention-deficit/ hyperactivity disorder (ADHD). However, these reports can have several problems because they are diverse, unstructured, subjective, and involve human errors. Additionally, physicians often do not read the entire report, and the number of reports is lower than that of diagnoses. Methods: We developed explainable predictive models for classifying IDs and ADHDs based on written reports to address these issues. The reports of 1,475 patients with IDs and ADHDs who underwent intelligence tests were used for the models. These models were developed by analyzing reports using natural language processing (NLP) and incorporating the physician’s diagnosis for each report. We selected n-gram features from the models’ results by extracting important features using SHapley Additive exPlanations and permutation importance to make the models explainable. Developing the n-gram feature-based original text search system compensated for the lack of human readability caused by NLP and enabled the reconstruction of human-readable texts from the selected n-gram features. Results: The maximum model accuracy was 0.92, and the 80 human-readable texts were restored from four models. Conclusion The results showed that the models could accurately classify IDs and ADHDs, even with a few reports. The models were also able to explain their predictions. The explainability-enhanced model can help physicians understand the classification process of IDs and ADHDs and provide evidence-based insights.

Background: Dementia is a multifaceted disorder that affects cognitive function, necessitating accurate diagnosis for effective management and treatment. Although the Mini-Mental State Examination (MMSE) is widely used to assess cognitive impairment, its standalone efficacy is debated. This study examined the effectiveness of the MMSE alone versus in combination with other cognitive assessments in predicting dementia diagnosis, with the aim of refining the diagnostic accuracy for dementia. Methods: A total of 2,863 participants with subjective cognitive complaints who underwent comprehensive neuropsychological assessments were included. We developed two random forest models: one using only the MMSE and another incorporating additional cognitive tests.These models were evaluated based on their accuracy, precision, recall, F1-score, and area under the receiver operating characteristic curve (AUC) on a 70:30 training-to-testing split. Results: The MMSE-alone model predicted dementia with an accuracy of 86% and AUC of 0.872. The expanded model demonstrated increased accuracy (88%) and an AUC of 0.934.Notably, 17.46% of the cases were reclassified from dementia to non-dementia category upon including additional tests. Higher educational level and younger age were associated with these shifts. Conclusion The findings suggest that although the MMSE is a valuable screening tool, it should not be used in isolation to determine dementia severity. The addition of diverse cognitive assessments can significantly enhance diagnostic precision, particularly in younger and more educated populations. Future diagnostic protocols should integrate multifaceted cognitive evaluations to reflect the complexity of dementia accurately.