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Objective@#To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).@*Methods@#The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg-1·d-1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D*) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively.@*Results@#The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm3 and (174.24±28.27)mm3, respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P<0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P>0.05). The D* values of the rhES group were (10.940±2.834)×10-3mm2/s and (12.940±2.801)×10-3mm2/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10-3mm2/s and (7.898±1.603)×10-3mm2/s of control group (P<0.05). Moreover, compared with control group, the D* value of rhES group was significantly lower in day 12 (6.848±1.460)×10-3mm2/s vs (9.950±2.596)×10-3mm2/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D* value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05).@*Conclusions@#IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D* and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.
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Objective To explore the relation of fat cells factor and insulin resistance in type 2 diabetes.Methods 60 patients were divided into obesity group, non-obese group and normal control group.To detect the FINs, FPG, TG, TC, LDL,HDL,APN,CTRP3,leptin and TNF-α, according to the formula of HOMA,to analyze the correlation between indicators.Results 1).Compared with normal control group, DM group significantly decrease serum APN, CTRP3 level, compared with non-obesity group, obesity group APN, CTRP3 level significantly decreased(P<0.05 or P<0.01).The leptin level elevated (P<0.05).2)APN concentration and age, BMI, FPG, TG, TC, LDL, FINs, HOMA-IR has negative correlation;CTRP3 andFPG,FINs, HOMA-negative correlation IR(P<0.05), TG was positively correlated (P<0.05);TNF-α and FPG and positively correlated (P< 0.05).Conclusions T2DM patients` serum APN, CTRP3 and high Leptin levels are closely associated with obesity, HOMA-IR, FPG and TG as an independent factor can be used as a new sensitive index of evaluating the degree of insulin resistance.
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AIM: To observe the influence of gold nanoparticles combined with Endostar (AuNPs-Endostar) on the melanoma lung metastasis of mice and the underlying mechanism.METHODS: C57BL/6 mice (n=24) were selected for constructing the model of spontaneous lung metastasis of melanoma B16-F10 cells.Subsequently, the mice were randomly divided into Endostar group, AuNPs group, AuNPs-Endostar group and model group.After the formation of melanoma, the mice in each group were injected with different drugs through tail vein for 0.1 mL daily.After 9 d, the mice were narcotized for cutting the tumors in situ.After the operation, they were raised for 2 weeks before killed for obtaining the lung tissues to observe the situation of the metastasis.HE staining was utilized for observing the necrosis status of the tumors in situ, while immunostaining was applied for testing the expression of CD31, carbonic anhydrase-IX (CA-IX), vimentin and zonula occludens-1 (ZO-1) in the tumors.RESULTS: Compared with model group, the pulmonary metastasis in the groups with medical treatment was obviously reduced.In AuNPs-Endostar group, the metastasis inhibition rate was the highest, and the tumor necrosis was also decreased obviously, with the significant reduction of CD31, CA-IX and vimentin expression in the tumors and significant increase in ZO-1 expression.CONCLUSION: Compared with using Endostar or AuNPs alone, the combination of AuNPs with Endostar significantly improves the curative effect of inhibiting the pulmonary metastasis of melanoma in the mice.The mechanism may be related to reducing the tumor angiogenesis, norma-lizing the blood vessels and improving tumor hypoxia, thus inhibiting the tumor epithelial-mesenchymal transition, increasing the tight junctions between tumor cells and decreasing the invasiveness.
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AIM:To investigate whether gold nanoparticles (GNPs) reverses adriamycin (ADM), resistance of human hepatocellular carcinoma drug-resistant cell line HepG2/ADM and to explore the potential mechanism.METH-ODS:The sensitivities of HepG2 cells and HepG2/ADM cells to ADM were tested by MTT assay before and after GNPs pretreatment.The apoptotic rate was examined by flow cytometry.The concentration of ADM in HepG2/ADM or HepG2 cells was determined by ultraviolet-visible spectrophotometer .The content of glutathione ( GSH ) in HepG2/ADM or HepG2 cells by DTNB method.RESULTS:The half maximal inhibitory concentrations ( IC50 ) of ADM for HepG2/ADM cells were(29.46 ±1.73) mg/L and (15.18 ±0.85) mg/L before and after GNPs pretreatment,respectively.The IC50 of ADM for HepG2 cells was (9.16 ±2.03) mg/L before pretreatment.The apoptotic rate in GNPs+ADM group was higher than that in ADM group ( P reduce the content of GSH and increase the concentration of ADM in HepG2/ADM cells.
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<p><b>OBJECTIVE</b>To investigate the efficacy and safety of precise laparoscopic Roux-en-Y gastric bypass(LRYGB) in the treatment of obesity and metabolic diseases.</p><p><b>METHODS</b>Clinical and follow-up data of obese patients underwent precise LRYGB in our department between June 2011 and April 2013 were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 140 obese patients were included in this study. All the precise LRYGB procedures were successfully performed with no conversion to open surgery or perioperative death. Average operation time was (138.0±21.3) min, postoperative hospital stay was (5.2±1.2) d. No severe complications was observed. The percentages of excess weight loss in 1, 3, 6, and 12 month after operation were (26.4±8.6)%, (53.3±6.7)%, (75.3±7.9)%, (78.5±8.5)%, respectively. The improvement rates of fatty liver, hyperlipidemia, hypertension and type 2 diabetes mellitus were 84.6%(33/39), 92.3%(12/13), 77.3%(17/22) and 82.4%(14/17).</p><p><b>CONCLUSIONS</b>Precise LRYGB is a modified and optimized traditional surgical technique which does not significantly increase the operative time. It is safe and feasible. The postoperative weight loss effect is significant and it can effectively improve the related co-morbidities.</p>
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Humans , Diabetes Mellitus, Type 2 , Gastric Bypass , Hypertension , Laparoscopy , Length of Stay , Metabolic Syndrome , Obesity , General Surgery , Retrospective Studies , Weight LossABSTRACT
Objective To study the effect of cisplatin on the hepatocellular carcinoma HepG2 cells by Atomic Force Microscopy (AFM), then analysis the changes of ultrastructural in HepG2 cells during apoptosis induced by cisplatin at nanoscale level. Methods HepG2 cells were treated with cisplatin for 24h and 48h. The ultrastructural change of cell surface was detected by AFM , the inhibitory rate and apoptotic rate of cell were examined by MTT and fow cytometry. Results AFM images showed that with the prolongation of cisplatin-inducing, the deformation change of HepG2 cells varying degree. The cells appeared larger pore size of cell membrane, the value of cell membrane particle sizes, Rp-v, Ra, Rq and Meant Ht were significant increased. The inhibitory rate and apoptotic rate were significant increased. Conclusions Cisplatin induced shrinkage in cell morphology, pore formation and roughness increasing in cell membrane, thereby inducing apoptosis in HepG2 cells.
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Thyroid hormone is an important hormone for regulating cell differentiation,growth and metabolism.Many studies have shown that thyroid hormone can induce turmor angiogenesis after binding with the integrin ανβ3 receptor at cell surface.Tetraiodothyroacetic acid is the analogue of thyroid hormone,and can inhibit tumor angiogenesis by inhibiting the binding of thyroid hormone with integrin ανβ3.Studying the role of thyroid hormone in promoting tumor angiogenesis may provide a new approach for molecular targeted therapy of tumor.
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<p><b>OBJECTIVE</b>To investigate an method for hepatic differentiation from embryonic stem cells (ES cells) in vitro and the resulting differentiation ratio, in order to develop a procedure for producing a new type of hepatocyte for hepatocyte replacement therapy in the treatment of liver failure.</p><p><b>METHODS</b>ES cells from Balb/C mice were cultured and maintained in an undifferentiated state in gelatin-coated dishes using Dulbecco's modified Eagle's medium (DMEM) containing 1000 U/ml leukemia inhibitory factor (LIF). Then, LIF was withdrawn from the DMEM to allow the ES cells to develop into embryonic bodies (EBs). EBs were plated onto tissue culture dishes, and growth factors such as acidicfibroblast growth factor (aFGF) and hepatocyte growth factor (HGF) were added to the medium to promote directional differentiation. The course of development and differentiation was observed dynamically using an inversion microscope. The expression of hepatic proteins, such as alpha-fetoprotein (AFP), albumin (ALB), cytokeratin 8 (CK8), cytokeratin 18 (CK18), in cytoplasm was analyzed by immunocytochemistry (ICC). The concentration of ALB in the medium was determined dynamically by radioimmunoassay (RIA).</p><p><b>RESULTS</b>ES cells replicated as clones, without differentiating, in DMEM containing LIF. They developed into EBs in medium without LIF. Our ICC assay showed that differentiating cells did not express hepatic proteins, such as AFP, ALB, CK8, and CK18 until day 7, day 9, day 11, and day 11, respectively (up to 2 days later when growth factors are not present). The concentration of AFP in the medium was first detected on day 8, at a concentration of 3.4 ng/ml, and increased to 22.8 ng/ml by day 15. The concentration of ALB in the medium was 0.2 micro g/ml on day 11, and increased to 2.2 micro g/ml by day 15. ALB-positive cells under ICC manifest morphological structures were consistent with normal mouse hepatocytes. The differentiation ratio of hepatocytes in the ES cell differentiation system was 30% on day 15 (significantly lower without the presence of growth factors).</p><p><b>CONCLUSIONS</b>ES cells can differentiate into mature hepatocytes. Growth factors, such as aFGF and HGF, can enhance this differentiation and produce sufficient numbers of functional hepatocytes. This method may be a reliable new way of differentiating ES cells into hepatocytes for use in replacement therapy in the treatment of liver failure.</p>
Subject(s)
Animals , Mice , Cell Differentiation , Physiology , Cells, Cultured , Embryo, Mammalian , Cell Biology , Hepatocytes , Cell Biology , Liver , Cell Biology , Mice, Inbred BALB C , Stem Cells , Cell BiologyABSTRACT
Interleukin-12 can induce the production of INF-?, up-regulate the inhibitive factor of angiogenesis such as IP-10, MIG, TIMP, TNF-?, down-regulate the induced factor of angiogenesis such as VEGF, bFGF, MMP, inhibit the angiogenesis of tumor together and accelerate the regression of tumor. Interleukin-12 can inhibit the angiogenesis of tumor, which is independent of the immune system.
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To cultivate clinical graduate students with high quality is the mentor's duty.Focus should be directed on cultivating their comprehensive abilities,which include clinical practice and scientific research abilities,and the cultivation of which is the currently radical problems facing the graduate students education.Only when the clinical graduate students lay emphasis on cultivation of their clinical practice abilities and comprehensive abilities,can they meet the requirement for medical workers with high quality.
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[Objective] To search a suitable preoperative intestinal cleansing method for the operation of colon and rectum. [Methods] A randomized controlled trial was applied in 70 cases before colic and rectal operations. Group A was give:n decoction of Folium Cassiae for oral use and saline enema and Group B was treated with saline enema only. The effect on intestinal cleansing was observed during the operation. [Results] In Group A, 26 cases were remarkably effective in intestinal cleansing, 8 effective, and 1 ineffective and 14, 16 and 5 in Group B respectively ( P
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AIM: To study the expression of MDM2 and muta nt-type P53 proteins in primary hepatocellular carcinoma(HCC). METHODS: Using immunohistochemical staining method(SP),the expression of mutant-t ype P53 and MDM2 proteins was examined in 55 cases of HCC,23 cases of correspond ing paracancerous tissues and 10 cases of normal hepatic tissues. RESULT S: The frequencies of MDM2 and P53 positive expression in HCC were 17/55 (30 9%) and 23/55 (41 8%), respectively. There was both positive expression of MDM2 and mutant-type P53 in 11 cases (20%) with HCC. Expression of MDM2 showed a significantly positive correlation with expression of mutant-type P53 (r=0 310,P