Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy

Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.

Mechanism of the inhibitory effect of galangin on hepatoma cells / 临床肝胆病杂志

The mortality rate of hepatocellular carcinoma (HCC) remains high, and although there have been several treatment methods, HCC patients still have poor treatment outcome and prognosis in clinical practice. Therefore, it is necessary to find a new drug for the treatment of HCC to improve patients’ survival rate. This article introduces a new antitumor drug, galangin, which can exert an antitumor effect by inhibiting cell proliferation, promoting apoptosis, inducing autophagy, and inhibiting metastasis. In addition, galangin can also inhibit angiogenesis in liver cancer, reverse multidrug resistance, and enhance the synergistic effect between drugs. Therefore, galangin is believed to have a promising future in clinical practice, and it is expected that more studies will focus on the anti-hepatoma cell mechanism of galangin to provide a scientific basis for the clinical translation of galangin.

Protective effect of necrostatin1 on the damage of pancreas islet cells induced by TNFα / 中南大学学报(医学版)

OBJECTIVES@#To investigate whether necrostatin-1 (Nec-1) can protect islet cells from the damage induced by TNF-α.@*METHODS@#After isolation and purification, the neonatal porcine islet cell clusters (NICCs) were divided into 3 groups (islets 10 000 IEQ/group): a Nec-1 group (Nec-1+TNF-α was added to the culture medium), a TNF-α group (TNF-α was added to the culture medium), and a control group (pure medium). The number of cells was observed after 48 h of co-culture. The cell death was evaluated by AO/EB staining. Insulin secretion and DNA of islets were detected by chemiluminescence and nucleic acid quantitative analysis. RT-PCR assay was used to examine the mRNA expressions of insulin gene, glueogan gene and somatostatin gene. Flow cytometry analysis was used to detect the viability of B cells.@*RESULTS@#The number of islets in Nec-1 group, TNF-α group and the control group were (8 425±2 187), (4 325±778), and (7 122±1 558) IEQ, respectively. Compared to the other two groups, the number of dead cells in TNF-α group was greatly increased. The insulin/DNA values in the Nec-1 group, TNF-α group and blank control group were (13.21±3.15), (2.47±0.45), and (7.44±0.97) mIU/mg, respectively. Compared to the TNF-α group and the control group, the mRNA relative expression levels of insulin gene (6.73±1.07), glucagon gene (10.13±1.98), somatostatin gene (8.57±1.11) were significantly increased in the Nec-1 group (all <0.05), the rate of live cells (97.32±1.87)% and live B cells (90.86±3.68)% were increased significantly in the Nec-1 group (all <0.05).@*CONCLUSIONS@#TNF-α can induce neonatal porcine islet cells damage, which is attenuated in the presence of Nec-1. Nec-1 can increase the content of endocrine cells in NICCs.

Multidisciplinary team case discussion on complex pancreatitis with pancreatic head mass / 中华胰腺病杂志

One patient with recurrent attacks of pancreatitis and pancreatic head mass had a long history of recurrent abdominal pain, abdominal distension, nausea and vomiting, and no significant alleviations were observed under non-surgical treatment in many hospitals. After the diagnosis and treatment by the multidisciplinary team of gastroenterology, hepatobiliary and pancreatic surgery, oncology, pathology, radiology and other departments of Third Xiangya Hospital of Central South University, the patient underwent pancreaticoduodenectomy to completely remove the painful lesion, without leaving histological basis for canceration caused by chronic inflammation. The safety of the surgery was greatly improved and no obvious complications were observed.

Visualization analysis for radiomics research based on knowledge mapping / 中南大学学报(医学版)

To illustrate the literature distribution, research power distribution, and research hotspots in the radiomics research by using knowledge mapping analysis, and to provide reference for relevant researchers.
 Methods: Bibliographies from literature regarding radiomics in Web of Science database were downloaded. BICOM 2.0.1 and SATI 3.2 were used to clean and caculate the frequency of publication year, journal, author, key word, and research institution. CiteSpace V4.4.R1 was used to build the knowledge map of scientific research collaboration network between countries/regions.Ucinet 6 was used to build the knowledge map of scientific research collaboration network between core authors and institutions. gCLUTO 1.0 was applied to construct high-frequency keywords bi-clustering map.
 Results: A total of 700 literature was screened. Since 2012 the number of publications has been growing rapidly year by year. The United States, China, and Netherlands were leaders in this field. There were 5 major scientific research institution cooperative groups and 10 major author cooperative groups. Eight research hotspots were clustered by using high-frequency key word bi-clustering analysis.
 Conclusion: Radiomics is a new field and develops very fast. More and more countries, research institutions, and researchers with multidisciplinary background are going to participate in this filed. New terminology and new methods are going to appear in the field.

Application of CT-based radiomics in differentiating primary gastric lymphoma from Borrmann type IV gastric cancer / 中南大学学报(医学版)

To explore the feasibility of CT-based image radiomics signature in identification of primary gastric lymphoma and Borrmann type IV gastric cancer.
 Methods: A retrospective analysis of 71 patients with primary gastric lymphoma or Borrmann type IV gastric cancer confirmed by pathology in our Hospital from January 2009 to April 2017 was performed. There were 28 patients with primary gastric lymphoma and 43 patients with Borrmann type IV gastric cancer. The feature extraction algorithm based on Matlab 2017a software was used to extract the features of image, and the logistic regression model was used to screen the features to establish radiomics signature. The CT sign diagnosis model was established, which included the periplasmic fat infiltration, softness of the stomach wall, abdominal lymph node and peripheral organ metastasis, ascites, mucosal white line sign and lesion thickness. The classification of the two models was evaluated by receiver operating characteristic curve.
 Results: A total of 32 3D features were extracted from CT image for each patients. Two features were found to be the most important differential diagnosis factors, and the radiomics signature was established. The CT sign diagnosis model consisted of ascites, periplasmic fat infiltration, stomach wall softness and mucosal white line. For the radiomics signature and the CT subjective finding model, the AUCs were 0.964 and 0.867 with the accuracy at 94.4% and 80.2%, the sensitivity at 93.0% and 74.4%, the specificity at 96.4% and 89.3%, respectively. After Delong test, the diagnostic efficacy of the radiomics signature was higher than the CT sign diagnosis model (P<0.001).
 Conclusion: CT-based image radiomics signature can accurately identify primary gastric lymphoma and Borrmann type IV gastric cancer, and can potentially provide important assistance in clinical diagnosis for the two diseases.

Combination of prostate imaging reporting and data system with the apparent diffusion coefficient map for the diagnosis of peripheral zone prostate cancer / 中南大学学报(医学版)

To explore the value of prostate imaging reporting and data system version 2 (PI-RADS V2) combined with quantitative parameters derived from apparent diffusion coefficient (ADC) map in the diagnosis of peripheral zone prostate cancer.
 Methods: A total of 50 patients who underwent prostate multiparametric MRI (mpMRI) with suspicious peripheral nodules were retrospectively enrolled, and all patients were biopsy-proven histologically. Two radiologists analyzed the position and category of peripheral zone lesions based on PI-RADS V2. Then 12 ADC quantitative parameters were calculated regarding each lesion on the ADC map by post-processing software. The lesions were divided into malignant group and benign group according to histopathological findings. The ADC quantitative parameters between groups were compared, and stepwise logistic regression analysis was used to build a discriminative model. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were performed to evaluate the diagnostic power and clinical benefit.
 Results: Twenty-eight peripheral zone prostate malignant lesions and 25 benign lesions were obtained finally. The area under the ROC curve, sensitivity and specificity to differentiate peripheral zone prostate malignant from benign lesions were as follows: 0.803, 60.71%, 92.00% (PI-RADS V2 score), 0.857, 89.29%, 76.00% (ADC model), and 0.891, 71.43%, 92.00% (combined model), respectively. The discriminative power of the combined model was significantly improved compared with PI-RADS V2 score (P=0.012). The combined model had relatively optimal overall net benefit, which outperformed the PI-RADS V2 score when threshold probability varied in the range of 0.05-0.27 and 0.46-0.81.
 Conclusion: PI-RADS V2 combined with quantitative analysis of ADC map improve the power in discriminating peripheral zone prostate cancer from benign lesions, and the clinical benefit as well.

Radiomics strategy based on cardiac magnetic resonance imaging cine sequence for assessing the severity of mitral value regurgitation / 中南大学学报(医学版)

To assess the performance of radiomics model based on cardiac magnetic resonance imaging (CMR) cine sequence for assessing the severity of mitral regurgitation.
 Methods: A total of 80 patients who underwent CMR and echocardiography examination were retrospectively enrolled, including 67 patients with no or slight mitral regurgitation and 13 patients with moderate or severe mitral regurgitation. The relative difference in average filtered gradient (RDAFG) of CMR cine sequence were generated, which were combined with minimum output sum of squared error tracker (MOSSE) to extract 25 radiomics features. After reducing feature dimensionality by principal component analysis (PCA) and oversampling the minority samples, the radiomics model was established using support vector machine (SVM). The performance of the model was assessed by receiver operating characteristic (ROC) curve.
 Results: There were significant differences (both P<0.01) of the 2-dimension radiomics features between the two groups. The best performance (area under the ROC curve) of the established radiomics model was 0.971, with sensitivity and specificity at 85.7% and 94.1%, respectively.
 Conclusion: The performance of the machine learning-based radiomics model derived from CMR cine sequence for assessing the severity of mitral regurgitation was excellent, which can facilitate the computer-aided diagnosis and treatment in the era of artificial intelligence.

CT-based estimation of liver function using arterial enhancement fraction in liver cirrhosis patients / 中南大学学报(医学版)

To explore the feasibility and clinical value of CT-based arterial enhancement fraction (AEF) for evaluating liver function in liver cirrhosis patients.
 Methods: Fifty-two patients with liver cirrhosis (Child-Pugh A, B, and C group included 13, 20, and 19 patients, respectively) and 17 patients without liver diseases as control were prospectively enrolled, respectively. All individuals underwent three-phase hepatic CT, and the color mapping of AEF were obtained in CT kinetics software, as well as the corresponding parameters, i.e., hepatic AEF (HAEF) and the ratio of HAEF to spleen AEF (H/S). The AEF parameters were compared among different groups, and the area under the receiver operating characteristic curve (AUROC) was calculated. The Spearman correlation analysis was performed between the AEF parameters and model for end-stage liver disease (MELD) score in liver cirrhosis patients.
 Results: The interobserver agreement of HAEF and H/S were perfect, and the intraclass correlation coefficient (ICC) were 0.918 (95% CI 0.871 to 0.949), 0.946 (95% CI 0.915 to 0.966), respectively. The HAEF and H/S among those groups were significant different (both P<0.001), and they elevated with the increase of Child-Pugh classification in liver cirrhosis patients (all P<0.05, except the H/S between Child-Pugh A and B). In all patients with liver cirrhosis, the AUROC of HAEF and H/S were 0.933 and 0.821 for Child-Pugh A, and were 0.925 and 0.915 for Child-Pugh C, respectively. The HAEF and H/S of patients with liver cirrhosis were significantly correlated with the MELD score (HAEF: r=0.752, P<0.001; H/S: r=0.676, P<0.001).
 Conclusion: CT-based AEF parameters including HAEF and H/S are closely associated with the severity and prognosis of patients with liver cirrhosis, which have the potential to estimate the liver function in liver cirrhosis patients quantitatively and effectively.

Application of intravoxel incoherent motion diffusion weighted imaging for assessment of early chronic allograft nephropathy / 中南大学学报(医学版)

To investigate the feasibility and clinical application of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) technique in non-invasive assessment for early chronic allograft nephropathy (CAN).
 Methods: A total of 23 renal allograft recipients were recruited from inpatients or outpatients according to the inclusion and exclusion criteria for this study. Recipients were divided into a CAN group (n=12, pathologically confirmed early CAN patients) and a control group (n=11, volunteers with long-term stable renal function). Abdominal MRI was performed on patients of renal allograft with a multi-b value DWI sequence. IVIM2b-new software was used for obtaining the IVIM-DWI quantitative parameter pseudo-color maps and the values of IVIM-DWI of renal parenchyma, including the pure diffusion coefficient (D), perfusion correlation diffusion coefficient (D*) and perfusion fraction (f). The IVIM quantitative parameters between the two groups were compared using independent sample t test. ROC analysis was performed when the differences in parameter were statistically significant and the area under curve (AUC) was calculated.
 Results: In IVIM bi-exponential analysis, The D value was significantly decreased in the CAN group compared with the control group (P0.05). The AUC of D value for distinguishing the early CAN from the control were 0.784 with sensitivity and specificity at 58.3% and 90.9%, respectively.
 Conclusion: The IVIM-DWI quantitative parameter D can non-invasively assess early CAN to some extent. IVIM-DWI technique is expected to be an effective, easy and non-invasive method to detect early CAN, and assist early diagnose as well as dynamically monitor CAN.

Construction of three-dimensional finite element model and biomechanical study on patient with with cervical spondylotic myelopathy / 中南大学学报(医学版)

To establish a three-dimensional finite element model (FEM) of the neck, to analyze the differences in neck biomechanics between patient with cervical spondylotic myelopathy (CSM) and healthy subject and to provide biomechanics basis for the pathogenesis of CSM.
 Methods: A patient with CSM was enrolled in a mechanical simulation experiment. Three-dimensional CT scan was performed, and three-dimensional FEM of the neck was constructed. A heathy subject was selected as a control according to the patient's age, gender, height, and weight. Three-dimensional FEM was used to compare the stress differences in the vertebral body, intervertebral disc, ligament and spinal cord under the normal stress of the cervical spine and the maximum stress of the posterior reclining motion.
 Results: Successfully constructed FEM model of CSM patient and control, and performed mechanical analysis, the most obvious difference in cervical vertebral body force was at C5-C6 segment in CSM patients. The maximum stress site of control and patient was at the anterior edge of the vertebral body. The maximum stress of the vertebral body in the CSM patient was less than that of the control. The stress distribution of the intervertebral disc was irregular in the CSM patient, and the maximum stress was concentrated on both sides of the posterior edge of the intervertebral disc. The stress distribution of the ligaments of the CSM patient was uneven. The maximum stress was in the posterior longitudinal ligament. The range of neck movement in extension of the CSM patient was restricted.
 Conclusion: Compared with the healthy subject, the balance of the vertebral body, intervertebral disc, ligament and limited range of motion of the CSM patient has been changed, which may be related to the mechanical pathogenesis of cervical spondylotic myelopathy.

Radiomics in predicting tumor molecular marker P63 for non-small cell lung cancer / 中南大学学报(医学版)

Objective:To establish a radiomics signature based on CT images of non-small cell lung cancer (NSCLC) to predict the expression of molecular marker P63.Methods:A total of 245 NSCLC patients who underwent CT scans were retrospectively included.All patients were confirmed by histopathological examinations and P63 expression were examined within 2 weeks after CT examination.Radiomics features were extracted by MaZda software and subjective image features were defined from original non-enhanced CT images.The Lasso-logistic regression model was used to select features and develop radiomics signature,subjective image features model,and combined diagnostic model.The predictive performance of each model was evaluated by the receiver operating characteristic (ROC) curve,and compared with Delong test.Results:Of the 245 patients,96 were P63 positive and 149 were P63 negative.The subjective image feature model consisted of 6 image features.Through feature selection,the radiomics signature consisted of 8 radiomics features.The area under the ROC curves of the subjective image feature model and the radiomics signature in predicting P63 expression statue were 0.700 and 0.755,respectively,without a significant difference (P＞0.05).The combined diagnostic model showed the best predictive power (AUC=0.817,P＜0.01).Conclusion:The radiomics-based CT scan images can predict the expression status of NSCLC molecular marker P63.The combination of the radiomics features and subjective image features can significantly improve the predictive performance of the predictive model,which may be helpful to provide a non-invasive way for understanding the molecular information for lung cancer cells.

Imaging study on the homing of regulatory T cells in humanized heterologous liver tissue transplan-tation mouse model / 中华核医学与分子影像杂志

Objective To explore the homing of DiR labeled regulatory T cells ( Tregs) in human-ized heterologous liver tissue transplantation mouse model. Methods The fluorescence intensities of Tregs labeled with different concentrations of DiR dye and different incubation times were measured, and the cell viability was measured by 3-( 4, 5-dimethylthiazol-2-yl )-5-( 3-carboxymethoxyphenyl )-2-( 4-sulfophenyl )-2H-tetrazolium ( MTS) assay to determine the optimal incubation time and dye concentration. The effect of DiR dye on the function and phenotype of Tregs was verified by flow cytometry. The xenogeneic liver tissue transplantation mouse model was constructed and the immune system was reconstituted. Small animal fluores-cence imaging was performed at different time points after infusion of Tregs. Immunohistochemistry analysis was used to analyze immune reconstitution and lymphocyte distribution in vivo. One-way analysis of variance and Dunnett-t test were used to analyze the data. Results With the increase of DiR concentration and incu-bation time, the fluorescence intensity of Tregs increased and gradually weakened after reaching the peak at 3 d. The cell viability of the 5. 00 μg/ml and 20. 00 μg/ml groups was significantly lower than that of the control group (culture medium) at various time points (F=120.142-182.025, t=9.969-19.329, all P<0. 05) . After incubation for 30 min and 60 min, the activity of Tregs was also significantly lower than that of the control group (F=21.826-301.968, t=6.897-40.016, all P<0.05). Tregs were finally co-incubated with DiR dye at a concentration of 2.50 μg/ml for 5 min, which was used further in vivo experiments. The flow cytometry showed that DiR dye did not affect the phenotype or the function of Tregs. The small animal fluorescence imaging showed that Tregs could locate in the graft area of mouse model. Immunohistochemical analysis showed that Tregs could improve lymphocyte infiltration induced by immune reconstitution. Conclu-sion After labeling Tregs with DiR dye, the distribution of Tregs can be directly observed by fluorescence imaging, which is a promising imaging method for Tregs tracer.

Radiomics and its advances in hepatocellular carcinoma / 中南大学学报(医学版)

Liver cancer is the second leading cause of cancer-related death worldwide,so early detection and prediction for response to treatment is of great benefit to hepatocellular carcinoma (HCC) patients.Currently,needle biopsy and conventional medical imaging play a significant and basic role in HCC patients' management,while those two approaches are limited in sample error and observerdependence.Radiomics can make up for this deficiency because it is an emerging non-invasive technic that is capable of getting comprehensive information relevant to tumor situation across spatial-temporal limitation.The basic procedure for radiomics includes image acquisition,region of interest segmentation and reconstruction,feature extraction,selection and classification,and model building and performance evaluation.The current advances and potential prospect of radiomics in HCC studies are involved in diagnosis,prediction for response to treatment,prognosis evaluation and radiogenomics.

Development of a radiomics signature to predict Ki-67 expression level in non-small cell lung cancer / 中南大学学报(医学版)

To develop a radiomics signature based on CT image features to estimate the expression level of Ki-67 in non-small cell lung cancer (NSCLC).
 Methods: A total of 108 NSCLC patients, who underwent non-enhanced and contrast-enhanced CT scan in our hospital from January 2014 to November 2017, were retrospectively analyzed. They were confirmed by histopathological examination and undergone Ki-67 expression level test within 2 weeks after CT examination. The non-enhanced and contrast-enhanced CT three-dimensional structural images of the lesions were manually delineated by MaZda software, and the texture features of the region of interest were extracted. Combination of feature selection and classification methods were used to build radiomics signatures, and the classification were assessed using misclassification rates. The MaZda software provides texture feature selection methods including mutual information (MI), Fisher coefficients (Fisher), classification error probability combined with average correlation coefficients (POE+ACC), and Fisher+POE+ACC+MI (FPM), and texture feature analysis including raw data analysis (RDA), principal component analysis (PCA), linear classification analysis (LDA) and nonlinear classification analysis (NDA).
 Results: Among the 108 patients, 50 cases were at high levels of Ki-67 expression and 58 cases were at low levels of Ki-67 expression, respectively. The differences of gender, age and pathological type between the two groups were statistically significant (P<0.05). The radiomics signature built by FPM feature selection combined with NDA feature analysis based on non-enhanced CT images achieved the best performance for predicting the level of Ki-67 with a misclassification rate of 14.81%. However, radiomics signature based on contrast-enhanced CT images did not reduce the misclassification rate.
 Conclusion: The radiomics signature based on conventional CT image texture features is helpful to predict the expression of Ki-67 in NSCLC lesions, which can provide a non-invasive technique for assessing the invasiveness and prognosis for NSCLC.

Value of multi-slice spiral CT image texture analysis in diagnosing lymphatic metastasis of rectal cancer / 中华放射学杂志

Objective To investigate the value of multi-slice spiral CT image texture analysis in differentiating metastatic (MLN) from non-metastatic lymph nodes (NLN) in patients with rectal cancer.Methods Thirty five patiets with rectal cancer who were pathologically confirmed by total mesorectum excision were included retrospectively,with regional lymph nodes (short-axis diameter of larger than 3 mm)found in preoperative CT images.All the patients underwent preoperative abdominal and pelvic dynamic contrast-enhanced CT scan.Regional lymph nodes were identified according to pathological findings,and were divided into MLN and NLN groups.The short-axis diameter,short-to long-axis diameter ratio of lymph nodes were manually measured and calculated,and the texture features,including skewness,kurtosis,variance,entropy and inverse difference moment,were analyzed.The above parameters between MLN and NLN groups were compared using independent sample t test or Mann-Whitney U test.ROC curve analysis was performed regarding the statistically significant parameters and the areas under curve (AUC) were calculated.Multivariate Logistic regression analysis was accomplished to obtain the independent predictive factor of diagnosing regional lymph nodes.Results A total of 68 regional lymph nodes were obtained and consisted of 31 MLNs and 37 NLNs.The short-axis diameter,kurtosis,and entropy of the MLN group were significantly higher than those of the NLN group (all P＜0.05).Whereas,the short-to long-axis diameter ratio,skewness,variance,and inverse difference moment did not differ significantly between the two groups (all P＞0.05).The AUC for distinguishing MLN from NLN of the short-axis diameter,kurtosis and entropy were 0.79,0.67,and 0.85,respectively.Multivariate logistic regression analysis showed that only entropy (odds ratio=8.48,95％ confidence interval was 3.01 to 23.92,P＜0.01) was screened out as the independent variable,which suggested that the entropy was the unique predictor for characterizing regional lymph nodes of rectal cancer.Conclusion Multi-slice spiral CT images texture analysis can facilitate the accurate differentiation between MLN and NLN in patients with rectal cancer,and especially the entropy has the optimal reference significance.

Effect of M2 macrophage against rejection on islet allografts in diabetic mice / 中南大学学报(医学版)

Objective:To explore the possibility of using peritoneal alternatively activated M2 macrophages to prevent rejection after islet allotransplantation in a murine model.Methods:Peritoneal monocytes from C57BL/6 mice were induced and modulated to M2 and M0 macrophages in vitro,then the phenotype of macrophage was assessed by flow cytometry.C57BL/6 mice were induced diabetic by streptozotocin (STZ) injection and transplanted with islets isolated from BALB/c mice under the left kidney capsule.The recipients were randomly divided to 3 groups (n=8).A total of 2.5× 106 M2 macrophages were injected intravenously at 0,3,7 d after transplantation in islet+M2 group;2.5×106 M0 macrophages were injected intravenously at 0,3,7 d after transplantation in islet+M0 group;the mice in islet+PBS group were injected with PBS.Blood glucose was monitored after transplantation.On day 10 after transplantation,2 recipients in each group were randomly selected and sacrificed,and the left kidneys were resected for pathological examination.Results:Achievement of euglycemia was significantly prolonged after islet transplantation in the islet+M2 group than that in the other two groups (P＜0.01).The median survival time of islet allografts in the islet+PBS group,the islet+M0 group,and the islet+M2 group were 6.5 (4-10),7.5 (4-10),and 24(＞ 15) d,respectively.Pathological examination also showed that the grafts in islet+M2 group remained an intact structure with positive insulin stain and no apparent lymphocytes infiltration,while the graft was rejected in other 2 groups with negative insulin stain and massive lymphocytes infiltration.Conclusion:Peritoneal alternatively activated M2 macrophages can prevent rejection after islet allotransplantation,prolong the survival time of islet allografts and enhance the tolerance of the recipient to blood glucose in mice.

The evaluation of 64-slice spiral CT perfusion to hepatic fibrosis of dog model and the correlation research with pathologic and VEGF change / 中国医师杂志

ObjectiveTo measure the perfusion parameters of liver fibrosis of dog model with 64-slice spiral CT,and compare with positive control to reflect the degree of liver fibrosis,and analyze the correlation with VEGF values.Methods Liver fibrosis was induced in dogs by intraperitoneal injection of CC14 and high fat diet.CT perfusion scan and liver biopsies were performed.The perfusion parameters were measured according to the liver fibrosis models,and the correlation with VEGF values was analyzed.ResultsThe animals in experimental group were successfully induced different degree of liver fibrosis.In normal group,the hepatic artery perfusion,portal vein perfusion and total hepatic blood flow were (28.25 ±2.19)ml/(min · 100 g),(53.53 ± 10.71)ml/(min · 100 g) and (81.78 ± 18.56) ml/(min · 100 g).The PVP and TLP values of the liver fibrosis models of 0 - 4 stages declined gradually,and it had statistical significance,while the HAP values increased.The PVP and TLP values were positive correlated with fibrosis stage.The VEGF values of the pathological models of 0 - 4 stages ascended significantly.Conclusions The dog liver fibrosis models that are similar to human hepatic fibrosis have been successfully induced by low dose CC14 and high fat diet.CT perfusion can be used to monitor the tendency of the hemodynamic in different degree of fibrosis.VEGF may play an important role during liver fibrogenesis.

Advance in the islet transplantation for the treatment of diabetes / 中华消化外科杂志

Islet transplantation is effective in treating diabetes, however, its clinical use is highly restricted by a series of influencing factors. This review elucidates the non-immune factors including islet purification, instant blood-mediated inflammatory response and revascularization deficit on the development of islet transplantation, and also highlights the application and perspective of islet xenotrasplantation in the treatment of diabetes.

Detection of the immunologic rejection after xeno-islet transplantation:a study by MR imaging enhanced with superparamagnetic iron oxide marking CD4+T cell antibody / 中华放射学杂志

Objective To evaluate the feasibility of the diagnosis of the early immunologic rejection after xeno-islet transplantation by MR imaging enhanced with superparamagnetic iron oxide(SPIO)marking CD4+T cell antibody.Methods Two thousand neonatal porcine islets(NPI)were transplanted under the left renal capsule of BALB/C nude mice.When the grafts could be observed bv MRI.107 human PBMC was intraperitoneal injected to nude mouse models to reconstitute the human immunologic system,20 mice were reconstituted.Before and 3,7,14 days after reconstitution of human immunologic system on BALB/C nude mice,MRI imaging Was performed half an hour after intravenous injection of nano-immunomagnetic beads via vena caudalis to observe the grafts'MRI signal.BALB/C nude mice were sacrificed after MRI scanning immediately,the histopathologic examination was assessed on grafts,the results were compared with MRI results.And calculate the sensitivity,specificity,Youden index number and coincidence of the MRI for immunologic rejection.Results Grafts can be observed bv MRI 3 weeks after islet cell transplantation (before immunologic rejection modeling),there is no abnormal MRI signal detected in nude mice'graft region after mierobeads injected.Seven days after building of immunologic rejection model,MRI hypo-signal in graft site is shown in the T2 WI sequence after nano-bioprober injected.Histopathologic assessments were employed on grafts in nude mice immediately(HE and immunohistochemistry staining),the results shown that there are a lot of T lymphocyts infiltrated in graft region.implying the occurrence of immunologic rejection.And the sensitivity,specificity,Youden index number and coincidence is:(72.96±0.24)%,100%,0.73±0.24,(88.46±0.13)%respectively.The correct Kappa between the MRI and the imunohistochemistry staining was 0.76.Conclusion The cellular immunological rejection to xeno-islet grarts can be assessed with nano-bioprobe with anti-CD4+ antibody MR imaging,real time,and noninvasively.