Objective To investigate the regulation of T cells in the process of liver regeneration using a model of mice after 70% liver resection.Methods We performed 70% hepatectomy in T-cell-deficient mice and control mice.The liver mass and body mass ratio, BrdU infiltration level, proliferating cell nuclear antigen (PCNA),expression of M phase marker protein p-HDAC3, and serum transaminase levels were measured.Results The recovery of liver mass and body mass ratio of thymus-deficient mice occurred significantly later than that of control mice.The peak time of BrdU infiltration levels and the expression of PCNA and p-HDAC3 in T-cell-deficient mice were later than in control mice, but the degree of liver injury was lower.Conclusion T cells are involved in the regulation of liver regeneration, and the absence of T cells delays the process of liver regeneration.

It has been well established that immune surveillance plays critical roles in preventing the occurrence and progression of tumor. More and more evidence in recent years showed the host anti-tumor immune responses also play important roles in the chemotherapy and radiotherapy of cancers. Our previous study found that tumor- targeting therapy of anti-HER2/neu mAb is mediated by CD8(+) T cell responses. However, we found here that enhancement of CD8(+) T cell responses by combination therapy with IL-15R/IL-15 fusion protein or anti-CD40, which are strong stimultors for T cell responses, failed to promote the tumor therapeutic effects of anti-HER2/neu mAb. Analysis of tumor microenviornment showed that tumor tissues were heavily infiltrated with the immunosuppressive macrophages and most tumor infiltrating T cells, especially CD8(+) T cells, expressed high level of inhibitory co-signaling receptor PD-1. These data suggest that tumor microenvironment is dominated by the immunosuppressive strategies, which thwart anti-tumor immune responses. Therefore, the successful tumor therapy should be the removal of inhibitory signals in the tumor microenvironment in combination with other therapeutic strategies.
Animals ; Antibodies, Monoclonal ; immunology ; therapeutic use ; Breast Neoplasms ; drug therapy ; immunology ; pathology ; Cell Line, Tumor ; Female ; Humans ; Immune Tolerance ; immunology ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Receptor, ErbB-2 ; immunology ; Tumor Microenvironment ; immunology

Objective:To explore the diagnostic and grading value of combination of 68Ga -1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide ( 68Ga-DOTA-TATE) and 18F-flurodeoxyglucose ( 18F-FDG) dual probes in multi-parameter positron emission tomography (PET)/magnetic resonance (MR) imaging in pancreatic neuroendocrine neoplasm (PNEN). Methods:From April 9th, 2020 to February 24th, 2022, in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, the clinical data and the imaging of 68Ga-DOTA-TATE PET/MR and 18F-FDG PET/MR of 59 patients with pancreatic tumors (27 male, 32 female, aged 22 to 75 years old(51.8±13.3) years old), confirmed by surgical or biopsy pathology were retrospectively analyzed. All the cases were divided into PNEN group (42 cases) and non-PNEN group (17 cases) according to pathological results. Among which 39 patients with PNET were further divided into grade 1 group (G1 group, 27 cases) and grade 2 group (G2 group, 12 cases). Non-zero parameters were selected via the least absolute shrinkage and selection operator (LASSO) regression approach, and a logistic regression model was established by combination of the selected features and the corresponding non-zero coefficients. The measurement data with non-normal distribution were compared by Mann-Whitney U test. The receiver operating characteristic (ROC) curve were used to detemine the optimal cut off value to assess the dignostic efficiency. Results:Compared with those of non-PNEN group, the parameters of PNEN group increased, which included maximum standard uptake value of 68Ga-DOTA-TATE(SUV Gmax, 46.70 (22.37, 76.35) vs. 7.12 (4.75, 8.64)), mean standard uptake value of 68Ga-DOTA-TATE(SUV Gmean, 25.50 (13.18, 43.90) vs. 3.65 (2.89, 4.69)), peak standard uptake value of 68Ga-DOTA-TATE (SUV Gpeak, 27.17 (12.39, 46.97) vs. 5.46 (4.12, 6.56)), total lesion somatostatin receptor (SSR) expression (TLSRE, 68.21 (32.52, 440.96) vs. 26.02 (14.87, 69.57)), SUV Gmax/maximum standard uptake value of 18F-FDG (SUV Fmax, 12.71 (3.80, 21.70) vs. 1.10 (0.52, 2.35)), tumor to background ratio of 68Ga-DOTA-TATE (TBR G, 13.31 (5.54, 22.38) vs. 1.57 (1.31, 2.66)), tumor to liver ratio of 68Ga-DOTA-TATE(T/L G, 6.54 (2.90, 9.63) vs. 0.74 (0.65, 0.94)), tumor to spleen ratio of 68Ga-DOTA-TATE (T/S G, 2.36 (0.97, 3.70) vs. 0.25 (0.23, 0.38)), tumor to mediastinum ratio of 68Ga-DOTA-TATE (T/M G, 104.41 (34.03, 206.52) vs. 16.00 (12.87, 21.46)), SUV Gmax/minimum apparent diffusion coeffecient (ADC min, 55.14 (22.50, 96.37) vs. 6.76 (4.39, 12.76)) and SUV Gmean/ADC min (34.57 (13.47, 55.13) vs. 3.57 (2.46, 6.81)), and the differences were statistically significant ( U=28.00, 25.00, 32.00, 198.00, 54.00, 31.00, 28.00, 19.00, 10.00, 56.00 and 44.00, all P<0.01). The area under the curve (AUC) and diagnostic accuracy of dual-probe PET/MR imaging in the diagnosis of PNEN and non-PNEN were 0.941 and 96.6%, respectively. The AUC and diagnostic accuracy of model Y 1 in the diagnosis of PNEN and non-PNEN were 0.959 and 96.6%, respectively. There was no significant difference in AUC between model Y 1 and dual-probe PET/MR imaging in PNEN diagnosis ( P>0.05), however combining model Y 1 could improve the accuracy of PNEN diagnosis (100.0%). Compared with those of PNET G1 group, the parameters of G2 Group were higher, which included the maximum diameter of tumor (2.69 cm (2.08 cm, 5.00 cm) vs. 1.50 cm (1.20 cm, 2.50 cm)), metabolic tumor volume (MTV, 7.56 mL (4.45 mL, 53.57 mL) vs. 2.16 mL (1.22 mL, 5.48 mL)), total lesion glycolysis (TLG, 22.24 (11.95, 189.85) vs. 3.81 (2.11, 18.67)), tumor to background ratio of 18F-FDG (TBR F, 2.94 (2.00, 3.96) vs. 1.48 (1.29, 3.72)), tumor to liver ratio of 18F-FDG (T/L F, 2.32 (1.35, 2.98) vs. 1.08 (0.90, 2.17)) and SSR-expressing tumor volume (SRETV, 8.00 (3.06, 40.00) vs. 1.91 (0.95, 4.88)), and the differences were statistically significant ( U=66.00、66.00、77.00、93.00、90.00、65.50, all P<0.05). The maximum diameter of tumor was the best single parameter for the differential diagnosis of PNET G2 and G1, AUC was 0.796 and the cutoff value was 1.90 cm. The model Y 2, which combined the maximum diameter of tumor and TBR G had an AUC of 0.835 for the differential diagnosis of PNET G2 and G1. There was no significant difference in AUC between the maximum diameter of tumor and model Y 2 ( P>0.05). However the combination of the maximum diameter of tumor and model Y 2 could improve the accuracy of differential diagnosis of PNET G2 and G1 (94.87%). Conclusion:The combination of multi-parameter of 68Ga-DOTA-TATE and dual-probe 18F-FDG PET/MR imaging can improve the diagnostic and grading accuracy of PNEN, which may be helpful in the selection of clinical treatment for patients.

Objective:To explore the diagnostic value of 18F-fluorodeoxyglucose (FDG) PET/MR imaging for liver metastasis. Methods:A retrospective analysis of 75 cases (46 males, 29 females; age (58.9±14.3) years) with suspected liver metastases from January 2020 to October 2020 in Ruijin Hospital were performed. All patients underwent PET/MR and enhanced upper abdominal CT scans. Diagnostic efficacies of enhanced CT, PET, MR and PET/MR for liver metastases (based on lesions and patients respectively) were calculated and compared (McNemar test).Results:A total of 306 liver lesions were detected in 75 patients, of which 179 lesions in 45 patients were confirmed as liver metastases through follow-up or pathology. In lesion-based analysis, the sensitivities of enhanced CT, PET, MR and PET/MR were 74.9%(134/179), 60.3%(108/179), 98.9%(177/179) and 100%(179/179), with specificities of 96.9%(123/127), 100%(127/127), 92.9%(118/127) and 92.1%(117/127), respectively. The diagnostic efficacy of PET/MR was significantly higher than that of enhanced CT and PET ( χ2 values: 51.000 and 81.000, both P<0.001), but there was no statistical difference between PET/MR and MR ( χ2=2.000, P=0.368). In patient-based analysis, the sensitivities of enhanced CT, PET, MR and PET/MR were 82.2%(37/45), 84.4%(38/45), 95.6%(43/45) and 100%(45/45), with specificities of 86.7%(26/30), 100%(30/30), 70.0%(21/30) and 70.0%(21/30), respectively. The diagnostic efficacies of enhanced CT and PET were statistically different from PET/MR ( χ2 values: 13.000 and 16.000, both P<0.05), but there was no statistical difference between MR and PET/MR ( χ2=2.000, P=0.368). Conclusions:Compared with enhanced CT, PET and MR, 18F-FDG PET/MR has a higher detective rate for liver metastases. The overall diagnostic efficacy of 18F-FDG PET/MR is better than enhanced CT and PET alone, but similar to MR.

Objective:To explore the added value of T 1-weighted stack-of-stars volumetric interpolated body examination (StarVIBE) sequence on PET/MR image quality. Methods:A retrospective analysis was performed on 60 patients (42 males, 18 females; age 11-86 (58±12) years) who underwent 18F-FDG PET/MR examination and with positive PET results in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from April 2020 to April 2021. All patients completed StarVIBE sequence collection, and volumetric interpolated body examination (VIBE) sequence was used as control. StarVIBE and VIBE sequence images were evaluated independently using five-point method by two physicians. The evaluation was carried out from six aspects: lesion display, lesion boundary display, vascular around lesions display, fusion level with PET image, image artifact and overall image quality. Wilcoxon signed rank test was used to compare the image quality of the two sequences, and Kappa test was performed to assess the consistency of the image quality scores between the two physicians. Results:There were 26 cases with cervical lesions, 14 cases with chest lesions, 7 cases with abdomen lesions and 13 cases with pelvic lesions. The scores of lesion display (4.0(3.8, 4.5) vs 3.5(3.0, 4.0)), lesion boundary display (4.0(4.0, 4.0) vs 3.0(3.0, 3.5)), vascular around lesions display (5.0(4.0, 5.0) vs 4.0(3.5, 4.5)), fusion level with PET image (5.0(5.0, 5.0) vs 4.5(4.0, 5.0)), image artifact (4.5(4.0, 5.0) vs 4.5(4.0, 5.0)) and overall image quality (5.0(4.0, 5.0) vs 4.0(4.0, 4.0)) of StarVIBE sequences were better than those of VIBE sequences ( z values: 3.77-6.54, all P<0.001). On the vascular around the lesions display, the scores of StarVIBE were significantly better than those of VIBE sequence in the neck (5.0(4.5, 5.0) vs 3.0(2.7, 3.5); z=4.49, P<0.001) and chest (4.5(4.3, 4.7) vs 4.0(3.6, 4.3); z=3.10, P=0.002). As for image quality, the scores of StarVIBE were also significantly better than those of VIBE in neck (5.0(4.5, 5.0) vs 4.0(3.7, 4.5); z=4.36, P<0.001) and chest (5.0(5.0, 5.0) vs 4.0(4.0, 4.5); z=3.02, P=0.003). In abdominal lesions, the score of StarVIBE was higher than that of VIBE in blood vessels (4.5(3.5, 5.0) vs 4.0(3.5, 4.5); z=2.07, P=0.038), and there was no difference between score of overall image quality (4.0(3.7, 4.5) vs 4.0(3.5, 4.5); z=0.27, P=0.785). The score of overall image quality of pelvic StarVIBE sequence was better than that of VIBE sequence (5.0(4.5, 5.0) vs 4.0(4.0, 4.5); z=2.12, P=0.034). Kappa value of image quality score between two physicians was 0.554, indicating moderate consistency. Conclusion:In whole-body PET/MR imaging, StarVIBE sequence can significantly improve the image quality of cervical, thoracic and pelvic lesions when comparing with VIBE sequence.

Objective To investigate the effect of enteral nutritional support beginning at different time on aspiration events and immune function in the early post-traumatic (within 14 days) period in patients with severe traumatic brain injury.Methods From June, 2018, to February, 2021, 75 patients with acute traumatic brain injury admitted in the Department of Neurosurgery of the Second People's Hospital of Lianyungang were randomly divided into early feeding group (24 to 48 hours, n=35) and delayed feeding group (48 to 120 hours, n=40). The 14-day reflux rate, aspiration rate, incidence of aspiration pneumonia, immune indexes and complications were compared between two groups.Results There was no significant difference in the reflux rate, aspiration rate and the incidence of aspiration pneumonia between the two groups (P > 0.05). The levels of IgG, IgA, and complements C3 and C4 were significantly higher in the early feeding group than in the delayed feeding group (|t| > 1.720, P<0.001). The incidence of non-aspiratory lung infections was significantly lower in the early feeding group than in the delayed feeding group (χ2=4.728, P<0.05).Conclusion Initiating enteral nutrition within 24 to 48 hours after injury may preserve immune function and reduce the incidence of non-aspiratory lung infections in patients with severe traumatic brain injury.