Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

To establish a medical imaging teacher competency model and evaluate its application value in group teaching for undergraduates.

Objective: To evaluate the image quality of novel dark-blood computed tomography angiography (CTA) imaging combined with deep learning reconstruction (DLR) compared to delayed-phase CTA images with hybrid iterative reconstruction (HIR), to visualize the cervical artery wall in patients with Takayasu arteritis (TAK). Materials and Methods: This prospective study continuously recruited 53 patients with TAK (mean age: 33.8 ± 10.2 years; 49 females) between January and July 2022 who underwent head-neck CTA scans. The arterial- and delayed-phase images were reconstructed using HIR and DLR. Subtracted images of the arterial-phase from the delayed-phase were then added to the original delayed-phase using a denoising filter to generate the final-dark-blood images. Qualitative image quality scores and quantitative parameters were obtained and compared among the three groups of images: Delayed-HIR, Dark-blood-HIR, and Dark-blood-DLR. Results: Compared to Delayed-HIR, Dark-blood-HIR images demonstrated higher qualitative scores in terms of vascular wall visualization and diagnostic confidence index (all P < 0.001). These qualitative scores further improved after applying DLR (Dark-blood-DLR compared to Dark-blood-HIR, all P < 0.001). Dark-blood DLR also showed higher scores for overall image noise than Dark-blood-HIR (P < 0.001). In the quantitative analysis, the contrast-to-noise ratio (CNR) values between the vessel wall and lumen for the bilateral common carotid arteries and brachiocephalic trunk were significantly higher on Darkblood-HIR images than on Delayed-HIR images (all P < 0.05). The CNR values were significantly higher for Dark-blood-DLR than for Dark-blood-HIR in all cervical arteries (all P < 0.001). Conclusion Compared with Delayed-HIR CTA, the dark-blood method combined with DLR improved CTA image quality and enhanced visualization of the cervical artery wall in patients with TAK.

Objective To investigate the effect of different radiation doses on the accuracy of iodine quantification and CT value of virtual monochromatic image with a muti-spectral CT iodine phantom using second-generation dual-layer detector spectral CT(DLCT).Methods The second-generation DLCT scan abdominal phantom was used,which consisted of six different concentrations of iodine rods at 4,8 and 12 g/L.The scan parameters were set at 100,120 and 140 kVp tube voltages,and six radiation exposure sequences were scanned at each tube voltage:5,10,15,20,25 and 30 mGy.Measure the iodine concentration value and the CT value at the single level of 50,70 and 100 keV,and calculate the absolute error value of iodine concentration and CT value under different radiation exposure.SPSS 22.0 software single factor analysis of variance was used to compare the difference between the io-dine concentration and the absolute error of CT value under different Radiation exposure,and LSD method was used to compare the two groups.Results The absolute error of CT value of 4 g/L iodine rod with 10～30 mGy scanning at 100 keV energy level was significantly higher than that of 12 g/L and 8 g/L(P＜0.05),and the absolute error of iodine concentration measurement of other iodine rods with different concentrations at different Radiation exposure had no statistical difference.Conclusions The second-generation double-layer detector spectral CT has high meas-urement stability for iodine concentration quantification and CT value accuracy under conditions of radiation dose greater than 5 mGy.

Objective:To investigate the feasibility of coronary CT angiography(CCTA)-feature tracking(FT) for assessing global and regional myocardial strain in patients with heart failure(HF).Methods:From July 2019 to December 2020, twenty-five patients diagnosed with HF from Peking Union Medical College Hospital were prospectively enrolled into the study. All patients underwent retrospective electrocardiogram-gated CCTA and cardiac MR (CMR) imaging within 7 days. CCTA-FT and CMR-FT were undertaken using cvi 42 dedicated commercial software to measure global and regional strain parameters, including global peak radial strain (GPRS), global peak circumferential strain (GPCS) and global peak longitudinal strain (GPLS), as well as peak radial strain (PRS), peak circumferential strain (PCS) and peak longitudinal strain (PLS) of left ventricular basal segment, middle segment and apical segment. Conventional left ventricular functional parameters were also calculated, including left ventricular ejection fraction (LVEF), left ventricular stroke volume (LVSV) and left ventricular mass index (LVMI). Paired t test or Wilcoxon signed-rank test was used to compare the differences of measurements between CCTA group and CMR group. Pearson or Spearman correlation analysis was used to analyze the correlation between the two groups. Inter-and intra-observer consistence in CCTA group was evaluated by intraclass correlation coefficient (ICC) analysis. Results:The effective radiation dose of CCTA examination was 6.00 (4.86,7.63) mSv. Inter-and intra-observer consistence in CCTA group was excellent, and the ICC value was 0.85-0.98. In the overall strain parameters, GPCS in CCTA group[-8.10%(-10.32%, -5.20%)] was significantly lower than that of CMR group[-8.49%(-13.79%, -5.95%)] ( Z=-2.15, P=0.031). There was no significant difference in GPRS and GPRS between the two measurement methods ( P>0.05). Strong correlations were observed between GPRS, GPCS and GPLS ( r=0.65, 0.63, 0.71,all P<0.001). For local strain parameters, PCS in the middle segment and apical segment of CCTA group were lower than those of CMR group ( Z=-2.17, -2.62, all P<0.05). There were no significant differences in PCS of basal segment, PRS and PLS of all segments between groups (all P>0.05). The PCS and PLS of basal segment, PRS of middle segment and PRS of apical segment were moderately correlated ( r=0.46, 0.52, 0.58, 0.53, P<0.05); The other local strain parameters were strongly correlated, the range of r value was from 0.64 to 0.70 (all P<0.001). For left ventricular functional parameters, LVEF, LVSV and LVMI showed no significant differences between groups ( P>0.05), and the correlation was extremely strong ( r=0.90, 0.89, 0.96, all P<0.001). Conclusions:The repeatability of CCTA-FT technique in measuring myocardial strain was good, and the correlation of parameters measured by CCTA-FT technique and CMR-FT technique was excellent. Therefore, CCTA-FT technique can be used as a new noninvasive and simple method to evaluate myocardial motor function.

Objective:To explore the feasibility in evaluating segmental extracellular volume (ECV) using dual-layer spectral detector CT in patients with heart failure with various percentages of delayed hyper-enhanced volume, using MRI as a reference.Methods:Twenty-seven patients with heart failure in Peking Union Medical College Hospital were prospectively enrolled in this study from July 2019 to January 2021. All the patients underwent both CT late iodine enhancement and MR late gadolinium enhancement imaging within a week. According to percentages of hyper-enhanced volume on cardiac MR image, myocardial segments were classified into 3 groups: 0-4% (group A), 5%-49% (group B) and 50%-100% (group C). ECV images were independently observed by 2 experienced radiologists. The correlation and agreement between CT-ECV and MRI-ECV for the whole myocardial assessment and for the segmental assessment were evaluated using Spearman correlation and Bland-Altman analysis. Inter-observer agreement was assessed using the ICC.Results:Of the 27 patients, 432 segments were analyzed, with 199 segments in group A, 151 segments in group B and 82 segments in group C. In the whole myocardial analysis, the CT-ECV and MRI-ECV were 32.25% (28.04%, 34.28%) and 32.27% (28.35%, 34.77%), respectively. A good correlation was found between CT-ECV and MRI-ECV ( r=0.969, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias (0.4%), with 95% limits of agreement of -6.9% to 7.8%. as for the segmental myocardial assessment, the CT-ECV was 28.23% (26.18%, 29.92%) for group A, 33.29% (30.16%, 35.96%) for group B and 40.22% (34.06%, 46.70%) for group C. There was statistically significant difference in ECV among three groups (all P<0.001). Good correlations between CT-ECV and MRI-ECV were found in group A ( r=0.614, P<0.001), group B ( r=0.852, P<0.001) and group C ( r=0.953, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias 2.0% (95% limits of agreement:-17.6%-21.6%) in group A, a small bias -0.4% (95% limits of agreement: -13.8%-12.9%) in group B and a small bias -1.8% (95% limits of agreement: -17.4%-13.9%) in group C. The ICC values between 2 observers were 0.877 and 0.945 on CT-ECV and MRI-ECV, respectively. Conclusions:The larger percentage of hyper-enhanced volume on cardiac MR image, the stronger correlation are between the CT-ECV and MRI-ECV. CT-ECV may be taken as an alternative tool for quantitative evaluation of myocardial tissue in patients with heart failure.

Objective:To investigate the benefits of artificial intelligence (AI)-based image optimization technique on image quality of coronary CT angiography (CCTA).Methods:Sixty patients, who were referred for CCTA, were prospectively enrolled between May and June 2018 in Peking Union Medical College Hospital and were randomly divided into two groups. Group A was scanned with a low tube voltage of 80 kVp and a reduced contrast media volume of lopamiro at 0.7 ml /kg and group B was scanned with a standard 120 kVp tube voltage and an injection of 70 ml lopamiro. According to the different reconstruction methods, group A was divided into two subgroups. The images of group A1 were reconstructed with iterative reconstruction (IR). IR and further AI-based image optimization were used in group A2. Group B was also reconstructed by IR. To evaluate image quality objectively, the mean attenuation of contrast-enhancement values, background noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured and calculated in the region of interests (ROIs) of the aortic root (Ao), left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA), respectively. In addition, the subjective evaluation was performed by two radiologists using Likert 4 scale (1 for excellent and 4 for poor) to evaluate the image quality of coronary artery branches and segments. The estimated radiation dose in terms of volume CT dose index (CTDI vol), dose length product (DLP) and effective dose (ED) was recorded and compared between group A and group B. Analyses of the differences between groups were compared with image quality, radiation dose by t test or Wilcoxon signed ranks test, and subjective assessments were compares with χ 2 test. Results:In terms of lumen enhancement, compared to group A2, there was no significant difference in CT value of each ROI ( P>0.05); CT value of group A1 and group A2 at Ao was significantly higher than that of group B ( P<0.01), but there was no significant difference in other ROI ( P>0.05). By comparing noise, SNR and CNR, it could be seen that compared to group B, A2 group optimized by AI had a significantly lower noise level at Ao than group B ( P<0.001), and there was no statistical difference in ROI for the rest (all P>0.05).SNR at Ao was significantly higher than that of group B ( P<0.001), and there was no statistical difference in ROI for the rest ( P>0.05).However, the CNR of group A2 was significantly higher than that of group B in all ROI ( P<0.001). Compared to the AI-optimized A2 group, the noise of A2 group was significantly lower than that of A1 group at all ROI, and SNR and CNR were significantly higher than that of A1 group ( P<0.001). The subjective evaluation results of coronary segments showed that image quality of group A2 and group B was significantly better than that of group A1 ( P=0.002,0.038). There was no significant difference between group A2 and group B ( P=0.543). The radiation dose indexes of CTDI vol, DLP and ED in group A were significantly lower than those in group B (all P<0.001). The ED was decreased by 70.4%. Meanwhile, the volume of contrast media in group A was reduced by 37.1% than that that in group B. Conclusion:Compared to conventional scanning, CCTA images optimized by AI technology improved subjective and objective image quality.

Objective:To evaluate the feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography.Methods:Fifty-six patients with suspected coronary artery disease were enrolled and randomly separated into two groups. All patients were scanned at 120 kVp in step-and-shoot mode using a dual-layer detector CT (IQon spectral CT). Patients were either injected with 18 ml high concentration contrast medium(400 mgl/ml) at 2 ml/s (group A) or 45 ml contrast medium (370 mgl/ml) at 4 ml/s (group B). Forty to 80 keV monoenergetic images with 10 keV increment and conventional image (group A2) were reconstructed for group A, conventional poly-energetic image was reconstructed for group B. Region of interest was placed on aorta root (AO), middle segment of left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) to measure the attenuation and noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image quality was assessed by two reviewers independently with a 4-point scale on image quality (1-undiagnostic,4-excellent). The objective and subjective image evaluation were compared using the Kruskal-Wallis test. The Steel Dwass was used for multiple comparisons between monoenergetic images in Group A and conventional images in Group B, after the Kruskal-Wallis test.Results:There were significant differences among the attenuation, noise, SNR and CNR of group B, group A2, and monoenergetic images(all P<0.001).The CT value in the aortic root was significantly higher at 40-50 keV monoenergetic images than that in group B(all P<0.05), and similarly, the CT value in LAD,LCX and RCA at 40 keV were superior than that in group B(all P<0.001). There was no significant difference in the noise of the aortic root among 40 keV image, group A2 and group B(all P>0.05),while the noise in the 50-80 keV monoenergetic images were significantly lower than that in Group B(all P<0.001). The SNR and CNR in the aortic root were significantly higher at 40-60 keV monoenergetic images than that in group B(all P<0.001).The SNR in LAD and RCA at 40，50 keV and the CNR in LAD and RCA at 40-60 keV were higher than that in group B(all P<0.01).The SNR at 40-60 keV and CNR at 40-70 keV in LCX were superior than that in group B(all P<0.05). There were significant differences among the subjective image quality score of group B, group A2, and monoenergetic images(all P<0.001).The subjective image quality score of 40，50 keV images were not significantly different from that in group B (all P>0.05),while the score in 60-80 keV image and group A2 were lower than that of Group B(all P<0.001). Conclusion:40，50 keV low monochromatic images derived from dual-layer spectral detect CT combined with high concentrated contrast media can provide comparable or superior image quality with double low scanning in CCTA study.

Objective: To evaluate the effects of early mobilization combined with occupational therapy on delirium of mechanical ventilated patients. Methods: Sixty-eight patients who were undergoing mechanical ventilation and met the inclusion as well as exclusion criteria were randomized into an intervention group (35 patients) and a control group (33 patients). Patients in both group were provided with ICU routine care to prevent delirium, while early mobilization combined with occupational therapy was given in intervention group. Incidence rate of delirium, length of delirium, dosage of sedation, length of mechanical ventilation, length of ICU stay and physical restraint rate were compared. Occurrence of adverse events during intervention was also observed. Results: In intervention group,the incidence rate of delirium was 25.71%(9/35), length of delirium was (1.69±2.98) days, dosage of propofol was (2 189.71±1 222.23) mg, length of ventilation was (4.86±1.31)days, and physical restraint rate was 43.64%(146/275), all of which were significantly better than those in control group, which were 53.28%(17/33), (2 736.36±1 298.99) mg, (5.88±1.52)days, 53.28%(160/254) (χ²=4.788, 7.251, t=3.910, 2.980, P<0.05 or 0.01). There was no unpredicted issue occurred during intervention. Conclusions Early mobilization combined with occupational therapy is feasible which could alleviate ICU delirium, reduce the dosage of sedation, the length of mechanical ventilation, and the physical restraint rate.