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

Objectives:To finely divide the aortic sinus into sections and accurately localize the coronary ostium through CARTO three-dimensional mapping,and to assess the clinical effects of treating aortic sinus cusps premature ventricular contraction(ASC-PVC)and the ablation risk in the corresponding area with zero X-ray radiofrequency ablation. Methods:A total of 66 patients who underwent radiofrequency ablation for ASC-PVC from January 2020 to January 2023 were included in this analysis,patients were divided into experimental group(n=34)and conventional group(n=32).In the conventional group,the CARTO 3 system was used to create an aortic sinus model through the conventional method.The earliest stimulating target was identified by using electrical stimulation mapping(ESM).Radiofrequency ablation treatment was performed after the distance between the target and the coronary ostium was precisely measured by coronary angiography through the hollow tube of the ablation catheter or coronary angiography tube.In the experimental group,the CARTO 3 system was used to build a model of the aortic sinus and the coronary ostium and aortic sinus were divided into sections.The earliest stimulating target was identified by ESM.After localizing coronary ostium through the impedance changing pattern on the ablation catheter tips,catheter ablation was performed with zero X-ray.The data regarding the impedance of the ablation catheter in the aortic sinus were collected.The total operative time,the operative time in the aortic sinus,contrast dosage,X-ray exposure time,immediate and short-term success rates of the operation and complication rates were compared between the two groups.Besides,the distribution of successfully ablated targets and their relationship with the risk of ablation were analyzed in both groups. Results:There was no significant statistical difference in the immediate and short-term success rates between the two groups(93.8%vs.94.1%;90.6%vs.88.2%,both P>0.05).The experimental group did not receive contrast agents during the operation,and the total operation time and intra-aortic sinus operation time in the experimental group were significantly shorter than those in the conventional group([58.76±4.94]min vs.[66.91±5.94]min,P<0.001;[43.12±4.49]min vs.[50.31±5.18]min,P<0.001).During the process of moving the ablation catheter from the intra-aortic sinus to the coronary artery opening and into the coronary artery,the impedance suddenly increased,which was significantly different from the impedance in other parts of the intra-aortic sinus(all P<0.001). Conclusions:Radiofrequency ablation of ASC-PVC with zero X-ray can simplify the procedures and shorten the operative time.The steep increase in impedance at the tip of the ablation catheter can be used as a basis for localizing the coronary ostium.Dividing the aortic sinus into sections allows a detailed assessment of the risk for ablation treatment at the targets.

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 provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated.Methods:This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tc m -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results:Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) ( P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI ( P = 0.04) or US ( P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions:4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.

Objective: To investigate the clinical significance of combined examinations for neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal occult blood (OB) in the differential diagnosis of Crohn′s disease and irritable bowel syndrome. Methods: A total of 129 patients with Crohn′s disease and 120 patients with irritable bowel syndrome from October 2014 to October 2017 in Changhai Hospital were enrolled in this study. The results of NLR, CRP, ESR and OB were recorded. Logistic regression was used to study the association of the four indicators. The combined impact of the four indicators was explored with multivariable regression. ROC curve was used to compare the diagnostic value of the combined examinations with the four indicators for Crohn′s disease. The diagnosis was performed by substituting the data of individual patient into regression model. Results: The levels of NLR, CRP, ESR and OB in Crohn′s disease group were higher than those in irritable bowel syndrome group (Z=-7.067--4.148, P＜0.01). The area under the curve of combined diagnostic indicator was 0.881, which was higher than that of single NLR, CRP, ESR or OB (0.759, 0.695, 0.652, 0.643) respectively (Z=3.19-5.60, P＜0.01). When the cutoff value was 0.498, the sensitivity was 79.1%, the specificity was 83.3% and the diagnostic accuracy was 81.1%. A patient who was not included within the statistical range of this experimental study was randomly assigned to the model and 0.831 of P value was obtained, which was higher than the cutoff value of 0.498, indicating that the patient suffered from Crohn′s disease with accuracy of 81.1%. Conclusion The logistic regression model established with the combined diagnostic indicators, which was formulated by examinations of NLR, CRP, ESR and OB, exhibited higher diagnostic value than any single indicator in the differential diagnosis of Crohn′s disease and irritable bowel syndrome.

PURPOSE: The data on the differences between sputum autoantibodies (Sp-Abs) and serum autoantibodies (Se-Abs) in reflection of autoimmune responses to lungs is still lacking. METHODS: Ten types of Abs were investigated in matched Se and Sp samples collected from recruited subjects. Correlations between Ab levels and airway inflammatory parameters and measures of pulmonary function were assessed. The network-based and inter-correlated analysis was performed to explore the patterns of Sp- and Se-Ab profiles. RESULTS: Fifty stable asthmatic patients and 24 healthy volunteers were recruited for our study, 15 with mild asthma, 18 with moderate asthma and 17 with severe asthma. The concentrations of Sp-Ab against U1 small nuclear ribonucleoprotein (Sp-anti-U1-SnRNP), Sp-Ab against Smith antigen and Se-Ab against thyroid peroxidase (anti-TPO) in severe asthmatics and Sp-anti-U1-SnRNP in moderate asthmatics were significantly higher compared to healthy controls and mild asthmatic subjects (P < 0.05). Sp-anti-U1-SnRNP levels were positively correlated with the dose of inhaled corticosteroids, Sp eosinophil counts and fractional exhaled nitric oxide (r = 0.326, P = 0.022; r = 0.356, P = 0.012; r = 0.241, P = 0.025, respectively) and negatively correlated with Sp neutrophil counts (r = −0.308, P = 0.031) with adjustment for age. Spearman's correlation matrix showed multiple inter-correlations among Sp-Abs and Se-Abs (P < 0.05) while only the levels of Ab against DNA topoisomerase and anti-TPO in Se were correlated with those Sp-Ab counterparts (P < 0.05). The network-based analysis defined 2 clusters: clusters 1 and 2 contained 10 Sp-Abs and 10 Se-Abs, respectively. CONCLUSIONS: This study observes that Sp-Abs are more associated with clinical parameters and the severity of disease in asthma compared to Se-Abs. Targeting on Sp-Abs which are the hallmark of the localized autoimmune event might help us better understand the role of autoimmunity in the pathological mechanism of asthma.
Adrenal Cortex Hormones ; Asthma ; Autoantibodies ; Autoimmunity ; DNA Topoisomerases, Type I ; Eosinophils ; Healthy Volunteers ; Humans ; Iodide Peroxidase ; Lung ; Neutrophils ; Nitric Oxide ; Ribonucleoproteins, Small Nuclear ; Sputum

Objective To evaluate the clinical efficacy of portal venous thrombolysis by way of TIPS.Methods The clinical data of 40 patients with portal venous system thrombosis treated by TIPS at our department from May 2012 to May 2018 were retrospectively analyzed.There were 34 cases of via catheterdirected thrombolysis(7 cases by catheter-directed thrombolysis alone and 27 cases by way of TIPS before catheter-directed thrombolysis),and 6 cases via pharmaco mechanical thrombectomy (AngioJet);the postoperative complications of the two methods were followed up.Results The portal vein was opened in all 40 patients,and there were no major complications during the operation.One patient in the catheter-directed thrombolysis group developed acute liver failure after surgery.In the mechanical thrombolysis group,1 patient was discharged after small intestinal necrosis resection and intestinal fistula reconstruction.After 6-24 months of postoperative follow-up,6 patients in the group of thrombolysis suffered from shunt canal stricture.Conclusions It is a safe and minimally invasive method to treat portal venous system thrombosis through TIPS.Mechanical thrombolysis is more direct and rapid than catheter thrombolysis.

Objective To evaluate the image quality and radiation dose of third-generation dual-source CT with tin filtration for spectral shaping and iterative reconstructions.Methods Thirty-five patients underwent low-dose CT (LDCT) for lung cancer screening on second-generation dual-source CT and follow-ups on third-generation dual-source CT. Image quality and radiation dose were compared between the two examinations.ResultsThe radiation dose of third-generation dual-source CT [dose-length product (DLP)(49.7±18.2)mGy·cm, effective dose (ED)(0.73±0.26)mSv] was lower than second-generation dual-source CT [DLP (86.37±13.44) mGy·cm, ED(1.20±0.42)mSv](t=6.01, P=0.000;t=6.57, P=0.000). The objective image noise of second-generation dual-source CT [(25.7±2.9)HU] was higher than that of third-generation dual-soure CT[(18.6±4.2)HU](t=5.24,P=0.000).The subjective image noise of second-generation dual-source CT [(4.60±0.49)scores] was significantly lower than that of third-generation dual-source CT [(4.80±0.40)scores] (t=4.15, P=0.000). Conclusion Chest CT for the detection of pulmonary nodules can be performed with third-generation dual-source CT that produces high image quality and low radiation dose when using a stellar infinity detector with spectral shaping.
Early Detection of Cancer ; methods ; Humans ; Lung Neoplasms ; diagnostic imaging ; Radiation Dosage ; Radiographic Image Interpretation, Computer-Assisted ; Thorax ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

Objective To evaluate clinical significance of platelet/lymphocyte ratio ( PLR) in the differentiation and severity determination of ulcerative colitis .Methods One hundred and ninety-two patients who sought medical care from June 2009 to June 2016, in Changhai Hospital , were enrolled as study subjects , of whom 97 were patients with ulcerative colitis and 95 were patients with irritable bowel syndrome .Differences in PLR between the 2 groups were analyzed and the sensitivity and specificity of PLR in the diag-nosis of ulcerative colitis were also evaluated .Through the modified Mayo score system , the activity of ulcerative colitis was evaluated , and pathological spreading site was determined by colonoscopy , and the correlation between PLR and disease activity and pathological spreading site was evaluated .Results As compared with those of the control group with irritable bowel syndrome , the while blood cell counts, blood platelet counts , PLR, the erythrocyte sedimentation rate and the C-reaction protein of the patients with ulcerative colitis were significantly increased, and statistical significance could be noted when comparisons were made between them (P<0.05).Statis-tical significance could be found in PLR differences between the ulcerative colitis patients and irritable bowel syndrome patients .ROC a-nalysis indicated that sensitivity and specificity of the PLR biomarker were respectively 67%and 58%.PLR data for the patients with irritable bowel syndrome and those with light , moderate and severe ulcerative colitis were 123.73 ±60.47, 114.32 ±43.66, 160.19 ± 56.52 and 253.35 ±86.82 respectively.Results indicated that there was no statistical significance in the clinical data between irritable bowel syndrome and light ulcerative colitis (P=0.54).However, statistical significance could be noted in the data between irritable bowel syndrome and moderate/severe ulcerative colitis(P<0.05).Statistical significance could all be seen in the differences of the clinical data between light, moderate and severe ulcerative colitis (P<0.05).But there was no statistical difference in PLR between different pathological lesions in the patients with ulcerative colitis (P>0.05).Conclusion PLR has certain clinical value and signifi-cance in the identification and diagnosis of ulcerative colitis and irritable bowel syndrome , and at the same time , it could evaluate the degree of inflammation of ulcerative colitis .

BACKGROUND:Poly(propylene fumarate) (PPF) can crosslink at room temperature, andβ-tricalcium phosphate (β-TCP) has good biocompatibility, but PPF/β-TCP composite bone cement has not yet been systematical y studied. OBJECTIVE:To prepare PPF/β-TCP composite bone cement and to explore its in vitro bioactivity and degradability. METHODS:β-TCP and PPF were respectively synthesized by liquid-phase precipitation and a two-step method, and PPF/β-TCP composite bone cement was prepared through mixing PPF withβ-TCP. The in vitro bioactivity of PPF/β-TCP was compared with the commercial poly(methyl methacrylate) (PMMA) through the ability of forming hydroxyapatite after immersed in simulated body fluid for 7 days. The in vitro degradability of PPF/β-TCP was studied via investigating the transformation of pH values, water uptake and mass loss, compressive strength and morphology at each time point. RESULTS AND CONCLUSION:There were hydroxyapatites formed on the PPF/β-TCP material, but none on the commercial PMMA material. The pH values of the PPF/β-TCP were stable in PBS for 63 days, indicating its degradation is moderate;the mass loss was up to 13.5%after 84 days. Scanning electron microscope displayed the degraded PPF/β-TCP surface, and its compressive strength was decreased gradual y, which good for the integrity and sustainability of mechanical properties during degradation. These results suggest that PPF/β-TCP bone cement holds mineralization and degradability in vitro.