Objective To develop a Gd-based MR probe containing arginine-glyeine-aspartic acid (RGD)motif to reveal integrin avβ3 receptor-expressed tumor.Methods Commercially available HYNICRGD conjugate with co-ligand EDDA was labeled with GdCl3,and the mixture was isolated and purified by solid phase extract(SPE)to get the entire probe Gd-EDDA-HYNIC-RGD.Human HCC cell line BEL-7402 was cultured and the cells harvested and suspended then subcutaneously inoculated into athymic nude mice for tumor growth.In vitro cell binding assay to integrin avβ3 receptor and cell viability experiments were conducted.Then in vivo,imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at baseline and time points of 0.30,60,90 mninutes and 24 hour post-intravenous injection(P.i.) via the tail vein.Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results.Results Gd-EDDA-HYNIC-RGD was successfully isolated by SPE and validity was verifled on signal enhancement througll in vitro and in vivo experiments.The T1 relaxation rate of the probe is 3.31 mmol/s:It is well tolerated to living cells when the concentration of the probe is below 0.1 μmol/ml;both BEL-7402 Hunlan Hepatocellular Carcinoma cell Iine and the tumor expressed avβ3receptor;The RGD-iigand was observed specificly binding with avβ3 receptor in vitro;The nude mice model bearing HHCC was well estabhshed.The signal intensity(SI)at the tumor site were 2247.6±39.0 at baseline and 2820.9±35.2 at 90 min p.i.respectively,the SI at 90min increased less than 25%of baseline,which is statistically different(t=-38.031,P＜0.05);while the SI at muscle site were 1824.2±32.8 and 1845.8±27.2 respectively,which is not statistically different(t=-1.424,P＞0.05);The signal to time curve for probe-administrated group is straightforward over time in the span of 0 to 90 minute p.i.while the control arms do not show such tendency.Conclusion Gd-EDDA-HYNIC-RGD has the potential to used as an MR probe detecting integrin avβ3 receptor-expressed tumor.This work may offer possibility of early detection and differentiation of specific tumors.

Objective To investigate the MRI and pathological features of different molecular subtypes of breast cancer.Methods The data of 202 patients who underwent primary breast cancer resection were retrospectively reviewed.All of the patients had MRI preoperatively.The molecular subtypes of breast cancer defined by immunohistochemistry were classified as basal-like,luminal and HER-2 overexpression.Morphology (including mass or non-mass like enhancement,shape and margin of masses,unifocal or multifocal masses) and enhancement characteristics on MRI,histologic types and grades of tumors were analyzed with Chi-square test,exact test,Fisher exact test,Kruskal-Wallis H test,and Wilcoxon test.Results Among the 202 patients,34 were basal-like,144 were luminal and 24 were HER-2 overexpression.The number of mass cases in each subtype was 29,133 and 19 respectively,making no significant difference (x2 =4.136,P =0.126).As for the shape of basal-like lesions,8 were round,19 were lobular and 2 were irregular,while this distribution was 23,58,52 in luminal subtype and 1,11,7 in HER-2 overexpression subtype (x2 =13.391,P ＜ 0.05).The margin was also strikingly different among three groups (smooth,spiculated,irregular):20,5,4 respectively in basal-like,27,53,53 respectively in luminal,and 4,7,8 respectively in HER-2 overexpression (x2 =28.515,P ＜ 0.01).52.6％ (10/19) of HER-2 overexpression cases were multifocal,while only 6.9％ (2/29) of luminal and 8.0％ (24/133) of basal-like ones were multifocal (x2 =16.140,P ＜ 0.01).Characteristics in dynamic contrast-enhanced MRI were statistically different,with homogeneous,heterogeneous,and rim enhancement 0,13,16 respectively in basal-like cases,28,93,11 respectively in luminal cases and 2,11,6 respectively in HER-2 overexpression cases (P ＜ 0.01).However,the difference for enhancement curve did not reach significance (P =0.457).Histologic types were significantly different among molecular subtypes (P ＜ 0.01).Luminal breast cancer consisted of various histologic types,32.6％ (47/144) of which were mixed type.The majority of the other two molecular subtypes were invasive ductal carcinoma.Furthermore,invasive ductal carcinomas with different molecular subtypes showed different histologic grades (Hc =30.014,P ＜ 0.01).Basal-like breast cancer was more likely associated with a higher grade of malignancy.Conclusions Different molecular subtypes of breast showed distinct MRI features and pathologic characteristics.MRI might be a useful tool for preoperative prediction of molecular subtypes of breast cancer.

BACKGROUND:Bone marrow mesenchymal stem cells have the chemotaxis and homing role that promotes immune system reconstruction, eliminate residual lesions and prevent recurrence in patients.
OBJECTIVE:To observe therapeutic effect of human bone marrow mesenchymal stem cells transplantation into high-metastatic potential hepatocellular carcinoma animal models on metastatic potential of high-metastatic potential hepatocellular carcinoma.
METHODS:Nude mouse models of high-metastatic potential hepatocellular carcinoma were established in vivo. In the experimental group, 5×105 cells were injected via the tail vein on day 7 after tumor inoculation, twice a week. In the control group, cellculture medium, 0.2 mL per mouse, was injected by the tail vein. After the start of the experiment, tumor volume was measured every 4 days. After tumor inoculation for 14 days, 21 days, 28 days, 35 days, 42 days, animal models were sacrificed, and then tumor mass and body mass were recorded to calculate the inhibition rate. PCR was employed to detect osteopontin, bone sialoprotein, and integrinα Ⅴ mRNA expression, as wel as bcl-2, bax, caspase3 mRNA expression.
RESULTS AND CONCLUSION:The inhibition rate of tumor mass showed the best results in week 3. As time went on, the tumor inhibition rate was gradual y decreased. Metastasis-related biological factors showed a gradual down-regulated trend, indicating the polarization of tumor apoptotic indexes, that is, anti-apoptotic factor, bcl-2, showed a decreasing trend, while apoptotic factors, bax and caspase3, appeared to have a gradual y increased trend. These findings suggest that human bone marrow mesenchymal stem cells effects to inhibit high-metastatic potential hepatocellular carcinoma animal models appear to vary with time. After human bone marrow mesenchymal stem cells transplantation for 3 weeks, the inhibition performance on high-metastatic potential hepatocellular carcinoma is the best, and then it weakens with time. Human bone marrow mesenchymal stem cells are found to inhibit the metastatic potential of hepatocellular carcinoma.

0.05).There was remarkable low signal intensity on T2-weighed imaging and no evident artifacts for molecular probe when the concentration of Fe2+ was 20 mg/L.The least number of labeled cells detected by MR in vitro was 6?106 when the concentration of Fe2+ was 20 mg/L.Conclusion:Molecular probe,SPIO-OCT,can effectively label breast cells which express SSTR.The reasonable Fe2+ concentration of labeled cells and imaging was 20 mg/L.There is a correlation between MR signal intensity in vitro and the number of labeled cells.

Objective To summarize the chest CT features of IgG4-related lung disease(IgG4-RLD).Methods The clinical data and chest CT findings of 10 patients with IgG4-RLD diagnosed by the pathological findings of lungs or bronchus were analyzed retrospectively,including masses,nodules,ground glass opacities,pulmonary interlobular septal thickening,bronchovascular bundle thickening,mediastinal lymph nodes enlargement and pleural involvement.Results There were two types of chest CT findings in 10 patients:(1 )Isolated mass/nodule type in 5 patients,presenting as a single lung mass (n＝3)and a single lung nodule (n＝2),and the lesions were in irregular shape, with shallow lobulated edges and burrs,with no mediastinal lymph nodes enlargement.(2)Interstitial thickening in 5 patients,presenting with thickening of pulmonary lobular septum(n＝5)and thickening of bronchovascular bundle(n＝4),multiple patchyground glass opacities(n＝3), consolidation(n＝3),mild mediastinum lymph nodes enlargement(n＝3),a little bilateral pleural effusion(n＝2)and nodular thickening of pleura(n＝2).Serum IgG4 level was increased in 4 cases.Conclusion Chest CT findings of IgG4-RLD can be classified into two types:solitary mass/nodule type and interstitial type.Combing the chest CT manifestation with clinical characteristics will improve the diagnostic accuracy of IgG4-RLD.

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.