Objective To investigate the effect and mechanism of methyltransferase-like 3(METTL3)on the pro-liferation,migration,and secretion of inflammatory factors by synovial fibroblasts from rheumatoid arthritis(RA).Methods The expression of METTL3 in synovial tissue(SF)from 25 patients with rheumatoid arthritis and 25 pa-tients with osteoarthritis was detected by RT-qPCR and immunohistochemistry,respectively.The concentration of RNA m6A was detected by ELISA.RA synovial fibroblasts were isolated and cultured,and divided into NC(nor-mal control)group,hi-METTL3(overexpression of METTL3)group,si-METTL3(knock-down METTL3)group,and STM2457(METTL3 specific inhibitor)intervention group.Cell proliferation was detected by CCK-8 method.Apoptosis was detected by flow cytometry.And the concentrations of interleukin-6(IL-6),interleukin-17A(IL-17A),receptor activator of nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in the superna-tant of cell culture were detected by ELISA.Results Compared with synovial tissue of osteoarthritis,the expres-sion of mRNA m6A and METTL3 in synovial tissue of RA significantly increased(P<0.05).After overexpression of METTL3,the expression of m6A in synovial fibroblasts increased.The proliferation and migration abilities of SF in hi-METTL3 group were significantly improved,and their apoptosis did not change significantly.The secretion of cytokines IL-6 and RANKL of SF in hi-METTL3 group significantly increased,while the OPG significantly de-creased(P<0.05).After interfering with METTL3 expression,the expression of m6A in synovial fibroblasts de-creased.Cell proliferation and migration of SF in siMETTL3 group significantly decreased.The secretion of cyto-kines IL-6 and RANKL significantly decreased,and OPG significantly increased(P<0.05).After intervention with METTL3 inhibitor STM2457,the proliferation and migration of synovial fibroblasts were significantly reduced,and the secretion of cytokines IL-6 and RANKL significantly reduced,and OPG significantly increased(P<0.05).There was no significant difference in the expression of IL-17A among each group.Conclusion METTL3 may promote the proliferation and migration of RA synovial fibroblasts,enhance the expression of IL-6 and RANKL,and inhibit the expression of OPG through RNA m6A methylation modification.

Objective:To establish a supportive and effective management mode of scientific research project application, promote the capacity building of scientific research in the hospital.Methods:Retrospective analysis was conducted on the national and provincial scientific research projects of Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical School from 2010 to 2019, and the practical effect of " point to point" management mode of scientific research project application was evaluated.Results:The funding rate of Xinhua Hospital, especially national scientific research projects and provincial talents projects, was greatly improved by adoption of the multi-dimensional " point to point" management mode of scientific research project application. The number of national scientific research projects increased from 34 (26.02 million) in 2010 to 72 (51.0851 million) in 2019.The number of provincial talents projects increased from 5 (1.05 million) in 2010 to 26 (6.5 million) in 2019.Conclusions:The " point to point" management mode of scientific research project application plays an important role in promoting the overall funding rate. Enhancement of comprehensive capacity of hospital scientific research can be achieved by further improvement of this management mode, early initiation and arrangement of funding application depending on the " close partner" entity, emphasizing scientific research talents cultivation.

Objective To prepare dual?modality single?photon emission computed tomography (SPECT)?MRI molecular nanoprobes targeting HAb18G/CD147 expressed on breast cancer cell membranes and investigate the physicochemical and biological properties in vitro. Methods Superparamagnetic iron oxide nanoparticles (SPIOs) were prepared by one?pot reaction method as described. The single?chain antibody fragments HAb18F(ab')2 were conjugated to SPIOs via chemical method and then labeled with 125I using Iodogen method. The final 125I?SPIO?HAbF18(ab')2 nanoprobes were purified. SPIOs or 125I?HAb18F(ab')2 were used as control. We carried preliminary evaluation on their physicochemical properties and biological characteristics in vitro: transmission electron microscope (TEM) and dynamic light scattering (DLS) were used to measure these nanoparticle sizes and the hydrodynamic diameters. The MRI T2 transverse relaxation efficiency of these nanoprobes at different Fe2+concentrations were measured with 1.5 T clinical MR scanner. The 125I?SPIO?HAb18F(ab')2 and 125I?HAb18F(ab')2 radiochemical purity were measured by thin layer chromatography and the radio chemical yield was calculated. We also conducted stability tests in vitro and octanol/water partition coefficient experiments. Two breast tumor cell lines, MDA?MB?231 (HAb18G?overexpressing cells,experimental group) and MDA?MB?468 (control), were used for assessment of cells viability at different Fe2 + concentrations (1, 5, 10, 20, 40 μg/ml) by methyl thiazolyl tetrazolium assay. Specific binding experiments in vitro included two parts:magnetic resonance imaging and radionuclide tests, the above?mentioned breast cancer cell lines were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes respectively and took MDA?MB?231 cells which were not treated as blank group. First comparing the MR signal intensity differences among experimental group, the control group and blank group, then calculated the rate of MRI signal changes;Two breast tumor cell lines, MDA?MB?231 and MDA?MB?468 were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes too, then measured radioactivity counting byγcounter at different time and calculated the cell binding rates, and did statistical analysis by using one?way ANOVA. Results The SPIOs were fairly homogeneous with an average core size of (10.32±1.30) nm;the SPIO and 125I?SPIO?HAb18F(ab')2 hydrodynamic diameter of 44.80 and 52.64 nm, and MRI scanning showed that the transverse relaxation efficiency of SPIO and 125I?SPIO?HAb18F(ab')2 were 38.79 and 106.73 mM-1 · s-1, respectively. The radio chemical yield of 125I?SPIO?HAbF18(ab')2 and 125I?HAb18F(ab')2 were 41.90% and 85.50%, respectively. The radio chemical yield of the two groups were >95%, suggesting well stability in vitro. The lipo?hydro partition coefficient values were -0.99 ± 0.03 and-1.49 ± 0.08, respectively, which demonstrated that they were both water?soluble substances. Different Fe2+concentrations (1,5,10,20,40μg/ml) of 125I?SPIO?HAb18F(ab')2 on breast cancer cell lines MDA?MB?231 and MDA?MB?468 showed no significant inhibition of cell proliferation (F values were 0.78, 0.66; P values were 0.58, 0.66). The cell?specific binding experiment showed: MRI signal intensity values on experimental group, the control group and the blank group were (1 670 ± 5), (1 930 ± 8), (2 349 ± 14), respectively, significant differences existed among these groups (F=4 408.48,P=0.000), the rate of signal intensity change of experimental group and the control group were 28.87%,17.78%. SPECT:MDA?MB?231 could uptake 125I?SPIO?HAb18F(ab')2, the cell binding rates were (6.52 ± 0.60)% and (10.52 ± 2.04)% in 20 min and 4 h, respectively.Conclusions Our results suggested that the dual?modality SPECT?MRI nanoprobes 125I?SPIO?HAb18F(ab')2 were prepared successfully with good physicochemical properties and biological characteristics in vitro. These dual?modality molecular imaging nano?probes may have potential to improvearly detection and diagnosis of HAb18G/CD147?expressing cancers and to facilitate the development of HAb18G/CD147?directed interventions.

Objective To study the effects of two different methods of high-pressure injections on imaging quality of synchronous left axillary artery and vein by using volume CT.Methods Forty seven patients who underwent left axillary vein and artery CTA examination study were analyzed retrospectively according to the contrast agent injection scheme and was divided into two groups A and B.Group A of 25 patients used protocol A,adopted clinical routine delay scanning method,via right elbow vein inject contrast medium.Group B of 22 patients used protocol B,adopted artery delayed imaging combined with vein direct imaging method,via right elbow vein,left radial vein inject contrast agent,respectively.Both values of CT and contrast to noise ratio (CNR) of two groups were compared,objective image quality was compared by two blinded readers.Mann Whiteny U test was used.Results The median of CT values for left axillary artery in group A was 151.9 HU.The median of CNR values for left axillary artery in group A was 7.4.The median of CT values for left axillary vein in group A was 116.0 HU.The median of CNR values for left axillary vein in group A was 3.83.The median of CT values for left axillary artery in group B was 348.8 HU.The median of CNR values for left axillary artery in group B was 25.3.The median of CT values for left axillary vein in group B was 497.0 HU.The median of CNR values for left axillary vein in group B was 35.4.Both values of CT and CNR in two groups showed significant difference (Z=-5.735,-5.799,-5.863 and-5.863,P＜0.01).All of the median scores in group B were greater than in group A(P＜0.01).Conclusion The enhancement effect of protocol B in the left axillary arteriovenous synchronous imaging is significantly higher than those of protocol A,and demonstrates clear image quality and clearer anatomic relationship.

Surgical resection is the primary treatment for locally advanced rectal cancer,but the local recurrence rate of surgical resection is still at a high level. Preoperative and postoperative chemoradiotherapy not only decreases the local recurrence rate of surgical resection,but also elevates the survival rate and life quality. Recently,adjuvant chemoradiotherapy has been applied as the standard therapy for locally advanced rectal cancer. The application of targeted drugs,new chemotherapy drugs and rapid changing radiotherapy technology provide more approaches to the treatment of locally advanced rectal cancer.

Objective To investigate the feasibility and effectiveness of inducing rabbit common carotid fusiform aneurysms via the common carotid extravascular digestion method. Methods Sixteen New Zealand white rabbits were randomly assigned into either an experiment group ( n=12 ) or a control group (n=4). Porcine pancreatic elastase 80-400 U were used to incubate and digest 2 to 4 cm segment of artery distal to the origin of right common carotid artery. One week after modeling,intravenous angiography was performed and the length and width of fusiform dilatation of common carotid artery were measured. The fusiform dilated artery was examined with hematoxylin and eosin staining and the vascular morphological changes were observed with scanning electron microscope. Isotonic saline solution was used to incubate common carotid arteries of the 4 New Zealand white rabbits in the control group. After one week,the same method was used to observe the lumen of common carotid artery and intimal changes. Results After the digestion of common carotid artery adventitia,the angiography of 12 New Zealand white rabbits of the experimental group revealed fusiform dilatation of common carotid artery of the 10 model rabbits. The widest diameter of the fusiform artery was 3. 70 ± 0. 32 mm;two rabbits had common carotid artery occlusion. Compared with the control group,the right common carotid artery diameter enlarged significantly in the experimental group (1. 80 ± 0. 16 mm,P<0. 01). The HE staining showed that the lumen widened, adventitia and media reduced. Scanning electron microscope showed intimal inflammatory injury and thrombus attachment. Conclusion Using porcine pancreatic elastase to digest the adventitia of common carotid artery can make fusiform dilatation of common carotid artery in rabbits. Using this method may effectively induce a model of fusiform aneurysm,and it has certain feasibility.

Objective To establish the carotid fusiform aneurysm model in rabbits carrying similar characteristics of human intracranial aneurysms by using induction method with porcine pancreatic elastase. Methods Twenty-five New Zealand white rabbits were randomly divided into normal control group (n=5), saline control group (n = 5) and study group (n = 15). The rabbits of the study group were randomly and equally subdivided into 7-day subgroup, 14-day subgroup and 21-day subgroup. By using induction method with porcine pancreatic elastase to digest right common carotid the fusiform aneurysm model was established in all the rabbits of the study group. DSA examination , HE staining and elastic fiber staining pathologic examination were carried out at 7, 14 and 21 days after the procedure to observe the imaging and pathologic changes of the fusiform aneurysm models. Results DSA angiography showed that the mean vascular diameters of the normal control group and the saline control group were (1.64 ± 0.17) mm and (1.66 ± 0.24) mm respectively. The mean length and width of the fusiform aneurysm of the 7-day subgroup, 14-day subgroup and 21-day subgroup were (19.33 ± 1.65) mm and (2.86 ± 0.21) mm, (19.66 ± 1.18) mm and (3.95 ± 0.54) mm, and (19.84 ± 0.82) mm and (4.03 ± 0.95) mm, respectively. Pathologically, rupture of internal elastic membrane, disordered structure of tunica media smooth muscle and distortion of cell shape were observed in the rabbits of 7-day subgroup. Gradually stabilized aneurysmal lumen intimal hyperplasia was seen in the rabbits of 14-day subgroup. Remarkable structure changes at the aneurysmal neck-cavity junction were found in the rabbits of 21-day subgroup. Elastic fiber staining demonstrated that strikingly thinned elastic layer was observed in the rabbits of 7-day subgroup, gradually thinning elastic layer at the aneurysmal neck-cavity junction was seen in the rabbits of 14-day subgroup, and the thinned elastic layer became stable in the rabbits of 21-day subgroup. Conclusion Using simple surgical method combined with porcine pancreatic elastase to digest vascular wall, carotid fusiform aneurysm models can be reliably established in New Zealand white rabbits which carry similar morphologic and pathologic characteristics of human intracranial aneurysms.

Cyclooxygenase-2 (COX-2),the rate-limited enzyme that converts arachidonic acid into prostaglandin,has been found overexpression in many malignant tumors.The overexpression of COX-2 plays an important role in tumor genesis and progression and is closely associated with tumor prognosis,so this enzyme has become one of the potential therapeutic targets.Experimental studies reveal that selective COX-2 inhibitors can enhance the tumor radiosensitivity through a variety of molecular pathways and have a protective effect for normal tissues.Selective COX-2 inhibitors are promising radiotherapy modifiers and the underlying molecular mechanisms still need to be further studied.

Objective To investigate the level of B7-H1 and its counter-receptor PD-1 expression in mDC and different subsets of T lymphocytes in HIV infected individuals in China and to analyze the correlation between the level of B7-H1/PD-1 and disease progression, and to demonstrate that PD-1/PD-L1-dependent inhibition is operating in HIV infected patients.Methods Percentage of B7-H1 and PD-1 expression in mDC, CD+4 T cells and CD+8 T cells from thirty-six untreated HIV infected patients and 20 health controls were selected and detected by flow-cytometry, its correlations with CD+4 T cell absolute counts and plasma viral loads were analyzed.Results The percentage of B7-H1 expression in mDC, CD+4 T cells and CD+8 T cells (mean 15.21, mean 20.63, mean 13.5)were higher than that of health controls (all P<0.05).The percentage of PD-1 expression in CD+4 T cells and CD+8 T cells (mean 17.91, mean 19.21)were higher than that of health controls (P<0.05, P<0.05). The level of B7-H1 and PD-1 expression were inversely correlated with CD+4 T-cell counts(mDC+B7-H1+:r=-0.647, P<0.01;CD+4B7-H1+:r=-0.489, P=0.002;CD+8B7-H1+:r=-0.372, P=0.026;CD+4PD-1+:r=-0.374, P=0.025;CD+8PD-1+:r=-0.455, P=0.005) and positively correlated with HIV viral load(mDC+B7-H1+:r=0.662, P<0.01;CD+4B7-H1+: r=0.426, P=0.01;CD+8B7-H1+:r=0.531, P=0.001;CD+4PD-1+:r=0.362, P=0.03;CD+8PD-1+:r=0.380, P=0.022).Conclusion The level of B7-H1 and PD-1 expression was associated with HIV disease progression, which provides a useful marker to define disease progression of HIV infection.

ObjectiveTo observe the effect of succus entericus reinfusion with continuous enteral nutrition on the barrier function of intestinal mucosa and nutritional status in patients with stomal type fistulas. Methods Sixteen patients with stomal type fistula from July 1995 to May 2008 were enrolled in the study. A]l patients met the following conditions: gut function returned normal; abdominal infection was controlled; total enteral nutrition was provided ; and the length of small intestine for succus entericus reinfusion was more than 50 cm. Intestinal mucosa was taken at 25 to 30 cm away from stoma of fistula by endoscope 0, 7, and 14 days after reinfusior. Hematoxylineosin staining was performed to count the number of intestinal intraepithelial lymphocytes (IIELS). In addition,proliferating cell nuclear antigen (PCNA) was measured with immunohistochemical staining. Serum protein levels were determined by immunonephelometry. ResultsThe percentage of IIELS in intestinal mucosa ( 19.06％ ±4.81％ vs. 12.81％ ±2.95％, P=0.000) and the percentage of PCNA positive cells ( 12.13％ ±4.33％ vs.6.44％ ± 2.34％, P =0.000) 14 days after succus entericus reinfusion were significantly higher than those on the day of reinfusion. Serum fibronectin level increased from ( 152.80 ± 16.50 ) to ( 227.05 ± 45.36 ) mg/L ( P =0.000), and transferring protein level increased from ( 2.16 ± 0.52 ) to ( 2.62 ± 0.41 ) g/L ( P =0.017 ) 14days after succus entericus reinfusion. ConclusionSuccus entericus reinfusion is effective in protecting the intestinal mucosa in patients with stomal type fistulas.