The pathogenesis of diabetic retinopathy is complicated.The vast network of multiple factors including unifying mechanism,inflammatory reaction,neuron degeneration and metabolic memory of glucose,and the four established pathogenic molecular pathways are hotspots of mechanism research for diabetic retinopathy.Nevertheless,these researches may be only one corner of the iceberg of DR mechanism,and we still face enormous challenges in DR mechanism research.Collaboration with multiple disciplines to study the relationship between DR and diabetes and other systemic diseases,search novel therapy targets may increase the result in an unexpected windfall for DR basic research.

Breast cancer is one of the most common malignancies happened in female patients.The incidence of breast cancer in Chinese females has increased in recently years.Human epidermal growth factor receptor-2 (HER-2) exhibits gene amplification or high expression of receptor protein in about one third of breast cancer patients.HER-2 positive breast cancer patients has poor prognosis,high risk of recurrence and short survival.Trastuzumab is a specific inhibitor of human epidermal growth factor receptor-2 [1],which has been widely used in the treatment of HER-2-positive breast cancer patients,and trastuzumab molecular targeting therapy compared with the traditional chemotherapy,with the advantages of high specificity and low toxicity.It changes the natural disease progression of patients with HER-2-positive breast cancer and prolongs the patient's survival time.This article will review the researches on the four aspects,which including the development and the application of trastuzumab in the treatment of HER-2 positive breast cancer.

Objective To observe effect of environmental enrichment on the learning and memory ability and the expressions of hypoxia inducible factor 1α (HIF-1a) and vascular endothelial growth factor (VEGF) in rats with chronic cerebral hypoperfusion.Methods A total of 40 rats were randomly divided into 3 groups: bilateral vascular occlusion (2VO) of the common carotid arteries group (n=14, 2VO group), 2VO + enriched environment (EE) group (n=14, 2VO+EE group) and sham group (n=12, SHAM group).Morris water maze, novel object recognition test, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), immunohistochemistry methods and Western blotting were used to detect changes in learning and memory ability of rats and HIF-1α and VEGF expression levels in hippocampus.Results Morris water maze showed that the escape latency was longer in the 2VO group than in the SHAM group at 3, 4 and 5 day during the training (all P＜0.05), while the 2VO+EE group spent significantly less time in finding the platform as compared with the 2VO group at 4 and 5 day (both P＜0.05).The time for space exploration in target quadrant was less in 2VO group than in SHAM group (P＜0.05), while it was longer in 2VO +EE group than in 2VO group (P＜0.05).Novel object recognition test showed that the 2VO operation impaired the priority index (PI) of time spending at exploring the novel object (P＜0.05), and environmental enrichment could improve the PI in 2VO group (P＜0.05).The real-time RT-PCR and Western blotting showed that the HIF-1α mRNA expression was higher in 2VO group than in SHAM group (P＜0.05).The VEGF mRNA and protein expressions were higher in 2VO+EE group than in 2VO group (both P＜0.05).The expression of HIF-1α in hippocampal CA1 area was higher in 2VO group than in SHAM group (P＜0.05).Conclusions Environmental enrichment can alleviate the damages of spatial and non-spatial learning and memory ability which are caused by chronic cerebral hypoperfusion.And HIF-1α and its downstream gene VEGF may be involved in the restoration of cognitive function by enriched environment.

Cation exchange (CX) reaction for the non-fluorescent ZnS nanocrystal clusters (NCCs) can be used to detect trace biomolecules . Nano clusters synthetized by hydrothermal synthesis are porous. So they can quickly release large amounts of Zn2+ from through cation exchange ( CX) reaction and nano cluster, generate fluorescent signal under the action of zinc reagent to detect fluorescence. The relationship between the release efficiency, target binding force of Zn2+ and its average diamete was investigated when the average diameter was 44 nm, 86 nm and 144 nm in this experiment. Results showed that the smallest nano cluster exhibited the highest cation exchange efficiency, and 71 percent of Zn2+ closed could be released by microwave radiation within 2 min. When the sandwich method of NCCs of 44-nm was used to detect immunoglobulin E (IgE) in a sandwich assay, the limit of detection (LOD) was 5 ng / L, which was 1000 times lower than that of ELISA. It turns out that CX for the ZnS NCCs is superior to the conventional signaling strategies in its high amplification efficiency, robustness, and biocompatibility.

Objective To establish the type Ⅱ collagen specific T cell line of Wistar rat and observe its effect on transferring arthritis.Methods The Wistar rats were immunized with emulsified chicken type Ⅱ collagen (CCⅡ) in complete Freund′s adjuvant by intradermal injection to induce the rat model of collagen induced arthritis (CIA).The lymphocytes were obtained from mesenteric lymph nodes of CIA rats,and the type Ⅱ collagen reactive T cell line was selected and propagated by CCⅡ stimulating in vitro .The proliferation response and phenotype were analyzed by 3 H TdR incorporation and fluorescence activated cell sorter (FACS).The onset of arthritis and pathological characteristic in ankle joints of recipient rats were observed with naked eye and histochemical examination.Anti CCⅡ antibody in serum was assayed by enzyme linked immunosorbent assay (ELISA).Results A T cell line was successfully established.The results of FACS labeled with fluorescent antibodies showed that 98 2% of the line cells were T cells,of which 89 7% were CD4 + T cells.The results of adoptive transfer showed that the incidence of arthritis was 50% when the injected cell number was 5?10 7,meanwhile the level of anti CCⅡ antibody in serum was elevated more than that of the control.Conclusion A cell line has been successfully established.The result of arthritis transferring by T cell line shows that the T cell plays a great role in the pathogenesis of CIA and provides a research datum for rheumatoid arthritis therapy with T cell vaccine.

Objective To evaluate the cardiac function in patients with chronic obstructive pulmonary disease ( COPD) by using echocardiography.Methods Three hundred and twenty eight COPD patients and 60 age and gender-matched healthy subjects ( control group ) were enrolled in the study. According to Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) criteria, patients were as classified as mild (n=102), moderate (n=85), severe (n=80) and very severe (61).All participants underwent conventional echocardiography and two dimensional-speckle tracking echocardiography (2D-STE) to assess cardiac function.Results The LVEF was reduced significantly, while the PASP was increased in severe and very severe COPD patients [(60.9 ±2.0)% and (59.4 ±2.8)%, t value:3.358, 4.859 to normal controls, 5.247, 6.641 to mild, 3.280, 4.863 to moderate, respectively, all P<0.001].The LA size was dilated in very severe COPD patients [(3.9 ±0.5) cm, t value: -2.407, -2.625, -2.071,-2.186, P<0.05 ] , and the RVEF was significantly less than those of the other patients [ ( 42.8 ± 7.3)%,t value: 6.357, 6.832, 5.581, 4.639, P<0.05 ] .The right ventricular FAC of moderate or severe COPD patients and the segmental and global LS of left and right ventricular in COPD patients were significantly lower than those in the normal controls, and which were gradually decreased as GOLD classification rising [ RVFAC, moderate: ( 37.7 ±2.0 )%, severe: ( 35.5 ±3.2 ) %, very severe:(34.0 ±3.1) %, t value: -4.616, -5.982, -7.195, respectively; LSLVg, moderate: ( -18.62 ± 1.76) %, severe: ( -17.15 ±0.73 ) %, very severe: ( -16.51 ±0.89 ) %, t value: -9.389,-15.494, -16.873, respectively;LSRVg, moderate:(-20.52 ±2.27) %, severe:(-18.84 ±1.38)%, very severe:(-16.82 ±1.10) %, t value:-8.555, -13.595, -18.499, respectively, all P<0.001].Besides, the FAC of COPD patients was positively correlated with the RVEF (r =0.676,P <0.05), while the RVLSg was negatively correlated with the FAC and RVEF (r=-0.677, -0.591,all P<0.05) .Conclusions There were left and right ventricular dysfunction in COPD patients, which decreased as GOLD classification upgraded. The FAC and 2D-STE can effectively detect the subtle abnormalities of regional and global ventricular function.

OBJECTIVETo investigate the expression of neural salient serine/arginine-rich protein 1 (NSSR1) in colorectal cancer.

METHODSRT-PCR, Western blot and immunohistochemical staining were used to detect the expression of NSSR1 mRNA and protein in different mouse tissues and human colorectal cancer, respectively.

RESULTSNSSR1 mRNA was expressed in mouse cerebrum, cerebellum, heart, liver, intestine, kidney and lung tissue, but NSSR1 protein was only expressed in neural tissues. In normal human intestinal mucosa, NSSR1 was expressed in the colorectal epithelial cells. In colorectal cancer, NSSR1 was highly expressed in the nucleus of tumor cells.

CONCLUSIONThe extensive expression of NSSR1 in colorectal cancer cells may hint it's roles in the biological function of colorectal cancer.

Animals ; Cell Cycle Proteins ; genetics ; metabolism ; Colon ; metabolism ; Colorectal Neoplasms ; metabolism ; Humans ; Mice ; Neoplasm Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; RNA-Binding Proteins ; genetics ; metabolism ; Rectum ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Serine-Arginine Splicing Factors

Objective To explore the method of demonstrating main operative section of facial recess approach with multi-slice CT by using double oblique muttiplanar reconstruction.MethodsSimilarly as surgical procedure of facial recess approach,30 (60 eras) normal temporal bones in cadavers were reconstructed to observe main operative sections and anatomical marks.Main images of operative section of facial recess approach were reconstructed using double oblique multiplanar reconstruction on multislice CT.With the reference of operative anatomical marks,the ratios of visibility of anatomical marks on the transverse plane,coronal plane,sagittal plane and double oblique were calculated and compared.The degree,of which major anatomical landmarks were displayed on the same plane ( axial,coronal,sagittal,or doubleoblique sagittal plane),was classified using the following criteria: level 4: 100％ of anatomical landmarks were presented in the same plane; level 3: 90％ to 99％ of anatomical landmarks were presented in the same plane; level 2: 80％ to 89％ of anatomical landmarks were presented in the same plane; level 1: 70％ to 79％ of anatomical landmarks were presented in the same plane ; level 0: ＜ 70％ of anatomical landmarks were presented in the same plane.Classification data were tested by chi-square test.Results Four key operative section were involved in facial recess approach,which were of oblique sagittal orientation.The central mark of the first key operative section was semicircular canal by using double oblique multi-planar reformation.On reconstructed images of the first key operative section,horizontal reference line was short process of incus,and the angle adjusting the reference line on the transverse plane was 22.15° ±5.22°.On the reconstructed images of the first key operative section,coronal reference line was tympanic segment of facial canal,and the angle adjusting the reference line on the coronal plane was 14.35° ± 4.02°.On the reconstructed images of the second key operative section,the central mark was fossa incudis,the horizontal reference line was short process of incus and the angle was 20.15° ± 5.52°,while the coronal reference line was tympanic segment of facial cana,and the angle was 13.15° ± 3.33°.On the reconstructed operative images of the third key section,the central mark was pyramidal eminence,the horizontal reference line was the horizontal portion of the facial nerve and the angle was 32.53° ±5.22°,while the coronal reference line was the tympanic segment of facial nerve,and the angle was 15.05° ± 4.43°.On the fourth reconstructed images of the key operative section,the central mark was the posterior border of round window,the horizontal reference line was the superior border of oval window,and the angle was 50.15° ± 8.02°,while the coronal reference line was the tympanic segment of facial nerve,and the angle was 15.25° ± 4.12°.For the four planes (double-oblique sagittal,axial,coronal,or sagittal plane),the results of the degree to which they could include the major anatomical landmarks in the same layer of the first section were: level 4 in 60 sides,level 2 in 12 sides and level 3 in 48 sides,level 2 in 15 sides and level 3 in 45 sides,level 3 in 10 sides and level 4 in 50 sides,respectively.The results of the second section were: level 4 in 60 sides,level 2 in 11 sides and level 3 in 49 sides,level 2 in 13 sides and level 3 in 47 sides,level 3 in 11 sides and level 4 in 49 sides,respectively.The results of the third section were: level 4 in 60 sides,level 2 in 10 sides and level 3 in 50 sides,level 2 in 11 sides and level 3 in 49 sides,level 3 in 9 sides and level 4 in 51 sides,respectively.The results of the fourth section were: level 4 in 60 sides,level 2 in 9 sides and level 3 in 51 sides,level 2 in 8 sides and level 3 in 52 sides,level 3 in 5 sides and level 4 in 55 sides,respectively.The four planes differed significantly in the degree to which they could include the major anatomical landmarks in the same layer ( x2 =123.3200,121.4231,122.4011,125.4213,all,P ＜ 0.05 ).The visibility ratio of every section is 100％ (60/60).Conclusion Double oblique multi-planar reformation is a new method to demonstrate landmarks of operative section of facial recess approach in one slice.The reconstructive images of operative section with double oblique multi-planer reconstruction may provide valuable information for operation.

Objective To investigate autophagy and proteasome system alteration in vivo and in vitro of diabetic nephropathy (DN) model rats.Methods Rat glomerular mesangial cells were primaryly cultured,and cell proliferation was tested by MTT assay.The mesangial cells were cultured under different concentrations of glucose (5.4 mmol/L for normal control and 30 mmol/L for high glucose) for 0,8,16,72 hours.The expression of autophagy (LC3) and proteasome (PSMAs) proteins was examined by Western blotting analysis.Spontaneous type 2 diabetes model OLETF and its normal control LETO rats were observed for 36 weeks.The levels of blood glucose and 24 hours urinary protein were evaluated in every 4 weeks.All the rats were sacrificed at the 36th week,and renal pathological changes were semi-quantitively analyzed.The expression of PSMAs and LC3 proteins was also examined in kidney cortex by Western blotting.Results Under high glucose concentrations,the abundance of PSMAs and LC3 proteins significantly reducedin the mesangial cells at 8 hours.There was no significant difference at other time points.The levels of blood glucose and 24 h urinary protein in OLETT rats exhibited progressive increase compared to those in LETO rats (all P＜0.01).And glomerular sclerosis index and tubulointerstitial injury index were significantly higher than those in LETO rats (all P＜0.01).The abundance of PSMAs proteins was significantly reduced in renal cortex of OLETF rats compared with LETO rats,while the abundance of LC3 proteins had no significant difference between two groups.Conclusion Proteolytic system dysfunction may play a role in pathogenesis of DN.