The repair of bone defects is heavily influenced by the dynamic osteogenic microenvironment. Static scaffolds constructed by traditional 3D printing technology cannot simulate the dynamic nature of the microenvironment during bone defect repair due to the fixed structure, uncontrollable release of active factors, and difficult regeneration of blood vessels, among other factors. Breaking through the limitations of these static scaffolds and realizing the intelligent and dynamic regulation of the osteogenic microenvironment is a key scientific issue in the field of bone tissue engineering. 4D printing technology combines the dynamic responsiveness of bone restoration materials with the concept of intelligent design to regulate the micro and macro structure of scaffolds. This technology provides a new method for bone tissue engineering by responding to endogenous and exogenous stimuli and creating a better osteogenic microenvironment through functionalized design, including drug delivery and antibacterial function. However, this technology currently suffers from challenges related to dynamic response material design, insufficient precision of printing technology, and mismatches between multi-stimulus response systems, metabolic rhythms of bone tissue, and functionalized composite scaffolds. Future research should focus on the development of smart response materials with excellent dynamic responses and bioactivity, the creation of new printing technologies, and the design of personalized and precise bone repair solutions. The aim of this paper is to review the current research status of 4D printing for bone tissue engineering in terms of material types, response mechanisms, and applications to provide a theoretical basis for the development and clinical application of functional bone repair materials in the future.

[摘 要] 目的：探讨乙醛脱氢酶1A1（ALDH1A1）mRNA负载树突状细胞（DC）疫苗体外诱导抗鼻咽癌干细胞免疫反应的能力。方法：体外转录ALDH1A1 mRNA并电转染至人外周血DC，构建ALDH1A1-DC疫苗，转染EGFP mRNA为对照。流式细胞术检测DC表型、淋巴细胞亚群、细胞毒性T 淋巴细胞（CTL）增殖和细胞因子分泌。分选ALDH+和ALDH- C666-1细胞，检测干细胞标志物（CD24、CD133）和干性基因（OCT4、SOX2、Nanog）的表达水平，采用CCK-8法评估ALDH1A1-DC疫苗诱导的特异性免疫杀伤能力。结果：EGFP-DC荧光表达率显著高于未转染DC（P < 0.000 1），ALDH1A1-DC抗原提呈分子HLA-ABC、共刺激分子CD86、CD40和CCR7表达与未转染DC相比显著增强（P = 0.001 3、P = 0.005 9、P = 0.000 4及P = 0.001 9）。与单独淋巴细胞组（T）及空载DC诱导的淋巴细胞组（DC-T）相比，ALDH1A1-DC诱导的CTL比例最高（均P < 0.000 1），分裂指数最高（P = 0.000 2、P = 0.000 3），且CD8+CD69+（P = 0.000 5、P < 0.000 1）和CD8+ IFN-γ+（P = 0.012 6、P = 0.001 9）细胞亚群比例均显著提高。ALDH1A1-DC-T细胞对ALDH+C666-1悬浮细胞球的杀伤效果显著优于ALDH-细胞球（P = 0.001 0），且与其他各组淋巴细胞相比表现出较强的抗ALDH+C666-1悬浮细胞球的免疫效应（P = 0.001 0，P < 0.000 1）。然而，HLA-ABC阻断后其对ALDH+C666-1细胞的特异性杀伤效应显著降低（P < 0.000 1）。结论：mRNA转染DC后可翻译蛋白并促进DC成熟，增强其诱导特异性CTL免疫反应的能力。

Pharmacist training in the pharmacy intravenous admixture service (PIVAS) center is a core component in ensuring the quality of finished infusions and medication safety. Based on the Quality Management Standard for Centralized Intravenous Admixture (2010) and the Notice on Issuing the Guidelines for the Construction and Management of Pharmacy Intravenous Admixture Services (Trial) (2021), the PIVAS center of Peking Union Medical College Hospital, guided by the concept of post competency, has developed a tiered training model tailored to the work requirements of different PIVAS positions (such as prescription review, drug admixture, and finished product verification). Concurrently, by integrating common admixture errors observed during training and routine practice, the program incorporates error-prone content into teaching priorities and dynamically adjusts the training plan, thereby providing a reference for the development of pharmacist training systems in China.

Objective: To investigate the status of latent tuberculosis infection（LTBI）among freshmen in middle schools and their willingness of preventive treatment in Yunyan District of Guiyang, so as to provide a reference for the prevention and control of tuberculosis in schools. Methods: The tuberculin skin test (TST) and X-ray scans were used to screen the TB infection of 13 915 freshmen in middle schools in Yunyan District of Guiyang in 2023, and a questionnaire survey on the willingness of accepting tuberculosis preventive treatment was conducted to LTBI patients. The χ 2 test and Fisher exact probability was conducted for the comparison of the rates among the groups. Results: Among the freshmen screened, the detection rate of LTBI was 3.29%. There were statistically significant difference in LTBI rates among freshmen of different genders (boys:2.87%, girls:3.81%), age groups (12-15 years old:3.31%, 16-17 years old:3.92%, 18-20 years old:1.91%), and school stages (junior high school:3.52%, ordinary high school:5.96%, vocational high school:2.29%)（ χ 2=9.59, 13.08, 54.30, P ＜0.01). A total of 356 LTBI freshmen completed questionnaire survey,and 299(83.99%) were willing to accept tuberculosis preventive treatment, but the actual number of LIBI freshman who underwent preventive treatment was zero. Those LTBI who had received Bacille Calmette Guérin(BCG) vaccine(86.97%) was higher in the reporting rates of being willing to accept preventive treatment than that of LTBI who had not received BCG vaccine( 75.79 %),the differences were statistically significant( χ 2=6.48， P <0.05). The main reasons for refusing preventive treatment was worry about adverse drug reactions(80.70%), social acceptance and the support of social institutions were needed most(85.96%). Conclusions The LTBI rate among freshmen in Yunyan District of GuiYang is higher. Although the freshmen with LTBI have a higher willingness to accept preventive treatment, however, no one has undergone preventive treatment. Corresponding measures need to be taken for improving the preventive treatment rate of LIBI freshmen.

Objective:To compare the dosimetric parameters under different incremental modes between intensity-modulated radiation therapy(IMRT)and volume rotation intensity-modulated therapy(VMAT)for the target area of large volume brain metastases(BMs),and to explore the better way of treating BMs based on hypofractionated stereotactic radiotherapy(HSRT)of linear accelerator.Methods:A total of 30 BMs patients who underwent IMRT at The 971th Hospital of Navy of the CPLA from 2020 to 2023 were selected.In the treatment planning system(TPS),three types of IMRT plans and VMAT plans were designed,which included uniformity plan(Planuniformity)of target area dose,uniform increased plan(Planuniform increased-dose)and incremental plan(Planincremental)within target area.In the inside of the target area,the target area of high dose(GTVh)was set,and Planuniform increased-dose and Planincremental were designed to aim at GTVh.The differences of the doses of three types of treatment plans included Planuniformity,Planuniform increased-dose and Planincremental,which were respectively designed by using IMRT and VMAT,were analyzed.The mean dose(Dmean)of the target area,the 50%and 2%exposed doses(D50%and D2%)of the target area were observed and compared.The conformity index(CI),homogeneity index(HI),gradient index(GI),and the volume percentage(V10 Gy-V40 Gy)that normal brain tissue received 10 Gy-40 Gy also were observed and compared.Results:Compared with Planuniformity of IMRT,the Dmean of GTV of Planuniform increased-dose and Planincremental of IMRT increased by 10.13%and 17.9%,with statistically significant differences(t=13.680,12.771,P＜0.05).D50%increased by 8.9%and 10.8%,with statistically significant differences(t=15.190,9.929,P＜0.05).D2%increased by 15.2%and 46.4%,with statistically significant differences(t=52.320,8.746,P＜0.05).There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of IMRT(P＞0.05).Compared with Planuniformity of VMAT,the Dmean of GTV of Planuniform increased-dose and Planincremental of VMAT increased by 10.53%and 21.23%,with statistically significant differences(t=18.641,15.461,P＜0.05),and D50%increased by 9.1%and 13.4%,with statistically significant differences(t=11.382,10.952,P＜0.05),and D2%increased by 16.4%and 48.8%,with statistically significant differences(t=56.471,8.685,P＜0.05),respectively.There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of VMAT(P＞0.05).The normal brain tissue V20 Gy,V30 Gy and V40 Gy of Planuniform increased-dose and Planincremental of IMRT were respectively less than those of VMAT,and the differences of them between IMRT and VMAT were significant(tPlan uniform increased-dose=2.112,2.215,2.444,tPlan incremental=2.323,2.939,3.145,P＜0.05).There were no statistically significant difference in D2%,Dmean,and D50%between IMRT and VMAT(P＞0.05).Conclusion:On the premise of ensuring the safety of normal brain tissue at the edge of the target area,the synchronously increasing of the central dose of the target area will not significantly increase the dose for normal brain tissue.Both IMRT and VMAT can meet the requirements of increment in the inside of the target area,and VMAT has slightly better increment and higher efficiency within target area.The incremental of VMAT target area is slightly better,which also has better efficiency,while the enhancement effect of the dose of target area of Planincremental is better than that of the Planuniform increased-dose.The Plan incremental of VMAT is more suitable for HSRT treatment for BMs.

Objective To develop a postoperative self-management question prompt list for adult liver transplant recipients and conduct preliminary application,aiming to provide an effective tool for facilitating their engagement in postoperative self-management.Methods From August to September 2024,the first draft of the postoperative self-management question prompt list for adult liver transplant recipients was developed through literature search and qualitative interviews,including 9 primary items and 50 secondary items.From October to November 2024,16 experts from Qingdao,Jinan,Beijing,and Fuzhou were interviewed on the Delphi method for 2 rounds to revise the question prompt list.From February to March 2025,19 patients after liver transplantation were selected for the preliminary application of the question prompt list.Results The response rates in the 2 rounds of consultations were both 100％and the authority coefficients of experts were both 0.88.The Kendall's W in the 2 rounds was 0.336 and 0.344(P＜0.001),respectively.The final question prompt list includes 9 primary items and 49 secondary items.The study showed that QPL demonstrated high clinical practicability in helping patients systematically understand the self-management framework after liver transplantation,promoting doctor-patient communication,and enhancing the initiative of self-management.Conclusion The question prompt list of postoperative self-management for adult liver transplant recipients established in this study is scientific,reliable,and practical,which is helpful for patients to obtain information about self-management from medical staff.

Objective To analyze the status quo and high-risk factors of hemorrhagic transformation(HT)in patients with acute cerebral infarction(ACI)treated with alteplase(rt-PA).Methods A total of 462 patients with ACI who were admitted to Hai'an People's Hospital and treated with rt-PA from June 2019 to June 2023 were retrospectively emrolled.According to the occurrence of HT,the patients were assigned to HT group(n=31)or non-HT group(n=431).The clinical data of the two groups were compared,and high-risk factors of HT in ACI patients treated with rt-PA were analyzed.Results The incidence of HT was 6.71%(31/462).Multivariate logistic analysis showed that increased systolic blood pressure(SBP),severe cerebral small vessel disease(CSVD),and increased neutrophil-to-lymphocyte ratio(NLR)were the high-risk factors of HT in patients with ACI after treatment with rt-PA(P＜0.05).Conclusion There is a high incidence of HT in patients with ACI after treatment with rt-PA,the levels of SBP,CSVD and NLR are the influencing factors,and they can provide a basis for prediction and clinical intervention.

Objective To explore the clinical efficacy and safety of salbutamol sulfate combined with reduced glutathione in treating acute exacerbation of chronic obstructive pulmonary disease(COPD)in the elderly.Methods A total of 103 elderly patients with acute exacerbation of COPD who were admitted to the Qingpu Branch of Zhongshan Hospital,Fudan University from January 2020 to June 2022 were randomly assigned to three groups.Control group 1(34 cases)received nebulized normal saline treatment.Control group 2(34 cases)received conventional treatment(e.g.,oxygen therapy,anti-infection,expectorant therapy,etc.)plus reduced glutathione.Treatment group(35 cases)received additional salbutamol sulfate on the basis of the control group 2.The treatment course was 12 days.Lung function,inflammatory factors,COPD assessment test,(CAT)score,BODE index,cardiopulmonary oxygenation function,6-minute walk test(6MWT)distance,modified medical research council dyspnea scale(mMRC)score,St.George's respiratory questionnaire(SGRQ)score,acute exacerbation frequency within 2 years,and adverse reactions were recorded.Results After treatment,the forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),and FEV1/FVC ratio in the treatment group were significantly higher than those in the control groups,while procalcitonin(PCT)and C-reactive protein(CRP)levels in the treatment group were significantly lower than those in the control groups(P<0.05).The treatment group exhibited lower CAT scores and BODE indices,higher maximal oxygen uptake(VO2max),metabolic equivalent of task at peak exercise(METspk),and respiratory frequency at peak exercise(RFEspk),longer 6MWT distances,and lower mMRC and SGRQ scores as compared with the control groups(P<0.05).The frequency of acute exacerbation in the treatment group was lower than that in the control groups at 6 months,1 year,and 2 years after treatment(P<0.05).No significant differences in adverse reactions were observed among the three groups(P>0.05).Conclusion The combination of salbutamol sulfate and reduced glutathione can significantly improve lung function,reduce inflammation,enhance quality of life,decrease acute exacerbation frequency,and demonstrate good safety in elderly patients with acute exacerbation of COPD.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.