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

Objective To investigate the relationships of expression of membrane palmitoylated protein 7(MPP7)in gastric cancer(GC)tissues with clinicopathological features and prognosis.Methods A total of 213 GC patients in the hospital from March 2018 to April 2020 were selected as research objects,and their tumor tissues and adjacent non-tumor tissues were collected.Immunohisto-chemistry(IHC)was used to detect the protein expression level of MPP7 in the tumor tissues and ad-jacent non-tumor tissues of GC patients,and the relationship between MPP7 and clinicopathological features was analyzed.The Kaplan-Meier survival curve was used to analyze the relationship between MPP7 expression and prognosis of GC patients.Univariate and multivariate Cox regression analyses were used to explore the relevant factors influencing the prognosis of GC patients.Results Compared with adjacent non-tumor tissues,MPP7 protein was significantly highly expressed in GC tissues(P＜0.05).Among GC patients,those with high MPP7 expression had significantly higher ratios of lymph node metastasis,Ⅲ to Ⅳ stages of cTNM staging,poor differentiation,and muscular layer invasion compared with those with low MPP7 expression(P＜0.001).Among the 156 patients with high MPP7 expression,the survival rate was 8.33％(13/156);among 57 patients with low MPP7 expression,the survival rate was 52.63％(30/57).The results of the Kaplan-Meier survival curve showed a significant difference in survival rates between the high MPP7 expression patients and the low MPP7 expression patients(Log-rank x2=54.333,P＜0.001).Compared with GC patients in the survival group,those in the death group had significantly higher ratios of lymph node metastasis,Ⅲ to Ⅳ stages of cTNM staging,poor differentiation,muscular layer invasion,and high MPP7 expression(P＜0.001).The results of multivariate Cox regression analysis showed that lymph node metastasis,Ⅲ to Ⅳ stages of cTNM staging,poor differentiation,muscular layer invasion,and high MPP7 expres-sion were all risk factors influencing the prognosis of GC patients(P＜0.05).Conclusion High MPP7 expression is closely related to the clinicopathological features and prognosis of GC patients,and it may serve as a potential biomarker for predicting GC progression and poor prognosis.

Objective To evaluate changes in morphology of the cesarean scar and uterus between one and two years after cesarean section using high-resolution, three dimensional T2-weighted sampling perfection with application optimized contrast using different flip angle evolutions Magnetic Resonance Imaging (3D T2w SPACE MRI). Methods This prospective study was performed to investigate morphological changes in the cesarean scars and uterus from one to two years after cesarean section using high-resolution, 3D T2w SPACE MRI. The healthy volunteers having no childbearing history were recruited as the controls. All data were measured by two experienced radiologists. All data with normal distribution between the one-year and two-year groups were compared using a paired-sample t test or independent t test. Results Finally, 46 women took a pelvic MR examination one year after cesarean section, and a subset of 15 completed the same examination again after two years of cesarean section. Both the uterine length and the anterior wall thickness after two years of cesarean section (5.75 ± 0.46 and 1.45 ± 0.35 cm) were significantly greater than those measured at one year (5.33 ± 0.59 and 1.25 ± 0.27 cm) (t = -2.363 and -2.175, P= 0.033 and 0.048). No significant difference was shown in myometrial thickness two years after cesarean section (1.45 ± 0.35 cm) with respect to the control group (1.58 ± 0.21 cm, P = 0.170). Nine women who underwent MRI twice were considered to have scar diverticula one year after cesarean section, and still had diverticula two years after cesarean section. The thickness, height, and width of the uterine scar showed no significant change from one to two years (all P > 0.05). Conclusions 3D T2w SPACE MRI provides overall morphologic details and shows dynamic changes in the scar and the uterus between one and two years after cesarean section. Scar morphology after cesarean section reached relatively stable one year after cesarean section, and uterine morphology was closer to normal two years after cesarean section.

Objective:To study the effect of low-dose aspirin combined with letrozole on serum visfatin, monocyte chemoattractant protein-1(MCP-1) and pregnancy rate in patients with polycystic ovary syndrome(PCOS).Methods:From November 2016 to November 2018, 110 patients with PCOS in the Third People's Hospital of Datong were selected.According to the random number table, they were divided into the observation group(60 cases) and the control group(50 cases). The control group was treated with letrozole, while the observation group was given letrozole combined with low-dose aspirin.The patients were continuously treated for 3 menstrual cycles.The changes of the serum visfatin, MCP-1, sex hormones, uterine artery blood flow before and after treatment, pregnancy and adverse reactions were compared between the two groups.Results:After treatment, the serum visfatin, MCP-1, testosterone (T), luteinizing hormone (LH), LH/follicular estrogen (FSH), uterine arterial pulsation index (PI) and resistance index (RI) in the observation group were (11.03±2.17)ng/mL, (99.31±14.50)ng/L, (1.57±0.29)mmol/L, (6.57±1.30)U/L, (1.16±0.22), (1.07±0.24), (0.41±0.08), respectively, which were significantly lower than those in the control group[(15.57±2.56)ng/mL, (121.29±20.37)ng/L, (1.78±0.32)mmol/L, (8.40±1.88)U/L, (1.50±0.27), (1.45±0.29), (0.57±0.11)], the differences were statistically significant( t=10.068, 6.593, 3.608, 6.012, 7.278, 7.521, 8.815, all P<0.05). The ovulation rate and pregnancy rate in the observation group were 81.67%(49/60) and 35.00%(21/60), respectively, which were significantly higher than those in the control group[64.00%(32/50), 18.00%(9/50)](χ 2=4.385, 3.974, all P<0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups( P>0.05). Conclusion:Low-dose aspirin combined with letrozole in the treatment of PCOS can effectively reduce the serum visfatin and MCP-1, regulate the sex hormones levels, improve uterine artery blood flow, improve pregnancy rate, and without increasing adverse drug reactions, so it's worthy of popularizing.

Chemical investigation of the roots of Uvaria grandiflora by repeated column chromatography(CC)over silica gel, ODS, Sephadex LH-20, and HPLC resulted in the isolation of twelve compounds. Their structures were identified as: epicatechin-(4β→1′, 2→O→2′)-phloroglucinol(1), proanthocyanidin A-1(2), proanthocyanidin A-2(3), epicatechin(4), phlorizin(5), eriodictyol(6), erythro-guaiacylglycerol-8-O-4′-(coniferyl alcohol)ether(7), threo-guaiacylglycerol-8-O-4′-(coniferyl alcohol)ether(8), erythro-guaiacylglycerol-8-O-4′-(sinapyl alcohol)ether(9), threo-syringylglycerol-8-O-4′-(sinapyl alcohol)ether(10), burselignan(11)and icariol A2(12). Compounds 1 to 12 were all isolated from this plant for the first time, and compound 1 was a new natural product.

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.

Objective To evaluate the feasibility of a low-dose one-stop-shop cardiac CT imaging protocol with third-generation dual-source CT (DSCT). Methods Totally 23 coronary artery disease (CAD) patients were prospectively enrolled between March to September in 2016. All patients underwent an ATP stress dynamic myocardial perfusion imaging (MPI) (data acquired prospectively ECG-triggered during end systole by table shuttle mode in 32 seconds) at 70 kV combined with prospectively ECG-triggered high-pitch coronary artery angiography (CCTA) on a third-generation DSCT system. Myocardial blood flow (MBF) was quantified and compared between perfusion normal and abnormal myocardial segments based on AHA-17-segment model. CCTA images were evaluated qualitatively based on SCCT-18-segment model and the effective dose(ED) was calculated. In patients with subsequent catheter coronary angiography (CCA) as reference,the diagnosis performance of MPI (for per-vessel ≥50% and ≥70% stenosis) and CCTA (for≥50% stenosis) were assessed. Results Of 23 patients who had completed the examination of ATP stress MPI plus CCTA,12 patients received follow-up CCA. At ATP stress MPI,77 segments (19.7%) in 13 patients (56.5%) had perfusion abnormalities. The MBF values of hypo-perfused myocardial segments decreased significantly compared with normal segments [(93±22)ml/(100 ml·min) vs. (147±27)ml/(100 ml·min);t=15.978,P=0.000]. At CCTA,93.9% (308/328) of the coronary segments had diagnostic image quality. With CCA as the reference standard,the per-vessel and per-segment sensitivity,specificity,and accuracy of CCTA for stenosis≥50% were 94.1%,93.5%,and 93.7% and 90.9%,97.8%,and 96.8%,and the per-vessel sensitivity,specificity and accuracy of ATP stress MPI for stenosis≥50% and ≥70% were 68.7%,100%,and 89.5% and 91.7%,100%,and 97.9%. The total ED of MPI and CCTA was (3.9±1.3) mSv [MPI:(3.5±1.2) mSv,CCTA:(0.3±0.1) mSv]. Conclusion The third-generation DSCT stress dynamic MPI at 70 kV combined with prospectively ECG-triggered high-pitch CCTA is a feasible and reliable tool for clinical diagnosis,with remarkably reduced radiation dose.
Computed Tomography Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Heart ; diagnostic imaging ; Humans ; Myocardial Perfusion Imaging ; Prospective Studies ; Radiation Dosage ; Sensitivity and Specificity

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 .

Objective To determine the utility of computed tomographic (CT) enteroclysis for characterization of the status of the anastomotic site in patients with Crohn's disease (CD) who have previously undergone ileocolic resection. Methods Totally 31 CD patients who had previously undergone ileocolic resection were enrolled in the study. After having been orally administered with isosmotic mannitol, the patients received CT scanning including plain scan, arterial phase scan, and portal venous phase scan. The abnormal CT findings were analyzed based on portal venous phase images. CT enteroclysis findings in 31 patients were evaluated by two radiologists in consensus. Endoscopic findings, histopathologic findings, and/or the Crohn's disease activity index (CDAI) were used as the reference criteria. Associations between CT enteroclysis findings and anastomotic site status were assessed. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT enteroclysis for the diagnosis of normal anastomosis versus anastomotic recurrence were estimated. Results Twenty-six cases and 5 cases were diagnosed as disease recurrence and normal anastomosis, respectively. In the disease recurrence group, 11 patients (42%) had lymphadenopathy (diameter＞ 1 cm) and 8 patients (31%) had peri-anastomotic fistulas, which were absent in normal anastomosis group, but the difference was not significant Anastomotic wall thickening more than 6 mm, marked mucosal enhancement, stratification, and peri-anastomotic stranding were found in 16 (62%), 19 (73%), 14 (54%), and 20 (77%) cases, respectively, in disease recurrence group, which were absent in normal anastomosis group ( all P ＜ 0.05 ). When the diagnosis of anastomotic recurrence was based on more than two of the following six variables, including lymphadenopathy, peri-anastomotic fistulas, anastomotic wall thickening more than 6 mm, marked mucosal enhancement, stratification, and peri-anastomotic stranding, its sensitivity, specificity, postive predictive value, negative predictive value, and accuracy yielded 88%, 100%, 100%, 63%, and 90%, respectively. The diagnostic accuracy of anostomotic stenosis with CT was only 53%. Conclusion CT enteroclysis yields objective and relatively specific morphologic criteria that help differentiate between recurrent disease and normal at the anastomotic site after ileocolic resection for CD.

Objective To discuss microvessel density (MVD) and expression of vascular endothelial growth factor(VEGF), androgen receptor(AR) in the prostates of men who received re-operation after TURP. Methods Fifty cases were performed re-TURP (re-TURP group) and the remaining 50 cases served as controls. 150 specimens were collected. Sections were stained for CD34 and VEGF, AR by immuno-histo-chemistry(S-P). Statistical analysis of the results was performed using t-test or Pearson Chi-Square test Results The expression of VEGF, AR and MVD were significantly higher in the re-TURP group compared to controls(P<0. 05),but in re-TURP group, difference in VEGF and AR expression as well as MVD were not found to be significantly different between the first and the second TURP(P>0.05). Conclusion Over expression of VEGF and AR as well as high MVD in prostatic tissue might play an important role in the pathological process of BPH after TURP.