Objective To develop a fluorescence signal activatable multifunctional molecular probe with theranostics function through combining ultrasmall gold nanorods(UGNRs) with fluorescein,and to evaluate its therapeutic effect on photothermal therapy (PTT) in breast cancer cells.Methods The UGNRs were synthesized by the one-pot seedless method,then the functionalized modification of UGNRs were conducted using cysteamine.Finally,the activatable ultrasmall gold nanorods (AUGNRs) were synthesized by amide condensation of —NH2 of cysteamine and —COOH of carboxylated fluorescein CyS.The cell uptake ability and GSH-mediated imaging ability of AUGNRs were studied using breast cancer 4T1 cells.4T1 cells co-cultured with AUGNRs were irradiated with 808 nm excitation light,and the PTT effects were assessed by MTT colorimetric staining and calcein-AM/PI staining.Results The AUGNRs were synthesized successfully,which could be uptaken by 4T1 cells quickly and efficiently,and could achieve intracellular glutathione (GSH) triggered fluorescence recovery.No obvious cytotoxicity of AUGNRs to 4T1 cells was observed in the co-cultivation.Moreover,obvious PTT effects could be induced by 808 nm laser,which could effectively kill 4T1 cancer cells.Conclusion The fluorescence signals of AUGNRs can be induced by intracellular GSH,and tumor cell destruction can be achieved by 808 laser-excitated PTT effects.

Objective To determine the utility of apparent diffusion coefficient (ADC) values as an objective method of early detection of traumatic brain injury of the mice models in hippocampus injury.Methods A total of 18 healthy male adult C57/BL6 mice were randomly divided into three groups according to the degree of injury:the mild group,severe group and control group.Conventional images,diffusion-weighted images,ADC were studied.The hippocampal were selected as the interesting area.ADC values were calculated and compared with those in control subjects after 6 h,12 h and 24 h.Student t test was performed for each region to compare the injury groups and the control.Results In control group both sides hippocampal ADC values had no differences(8.65±0.26 and 8.77±0.12) × 10-4 mm2/s,P＞0.05.Abnormalities were detected on ADC values,compared with conventional images in the injury groups.ADC values in mild group and severe group were significantly different from those of control group(6 h ADC values were (8.70±0.50) × 10-4 mm2/s,(6.13± 0.11) × 10-4 mm2/s,and (3.16±0.78) × 10-4 mm2/s in control,mild and severe group respectively),(12 h ADC values (8.23±0.61)× 10-4 mm2/s,(5.92 ± 0.27) × 10-4 mm2/s and (2.64±0.65) × 10-4 mm2/s) and (24 h ADC values (9.01±0.14) × 10-4 mm2/s,(5.99± 0.13)×10-4 mm2/s and (2.58±0.42)×10-4 mm2/s),P＜0.05.Conclusion There are differences among the ADC values on differcnt types of hippocampal brain injury mouse-model.ADC values can identify the degree of damage on brain injury and can detect early craniocerebral injury.

Objective Applying diffusion weighted image (DWI) and apparent diffusion coefficient (ADC) to analyze brain injury caused by hypoxic-ischemic encephalopathy (HIE) in term neonates.Methods From June 1,2010 to January 5,2011,thirty-eight full term neonates with HIE were hospitalized in the Second Hospital of Tianjin Medical University.Those with nervous system diseases were excluded.The 38 cases were divided to mild HIE group (n=24) and moderate-to-severe HIE group (n=14).The control group included 10 normal full term neonates without history of asphyxia.All babies were scanned by magnetic resonance imaging (MRI).Spin echo-echo planar imaging sequence was used for DWI images.ADC values of nine regions (frontal lobe gray matter,frontal white matter,parietal gray matter,parietal white matter,corona radiata,caudate nucleus,putamen,posterior limb of the internal capsule and thalamus) were measured.MRI and DWI images were compared.ADC values were compared by analysis of variance and Student-Newman-Keuls test.Results ADC values of the nine indicated regions (frontal lobe gray matter,frontal white matter,parietal gray matter,parietal white matter,corona radiata,caudate nucleus,putamen,posterior limb of the internal capsule and thalamus) were (1.37±0.07),(1.81±0.12),(1.35±0.10),(1.84±0.09),(1.23±0.11),(1.28±0.09),(1.18±0.08),(1.05±0.07) and (1.15±0.08) ×10-3 mm2/s in control group,(1.28±0.11),(1.60±0.15),(1.27±0.09),(1.59±0.20),(1.19±0.15),(1.19±0.13),(1.11±0.09),(0.97±0.11) and (1.06±0.12) ×10-3 mm2/s in mild HIE group,and (1.18±0.14),(1.51±0.22),(1.19±0.09),(1.56±0.19),(1.03±0.16),(1.08±0.07),(1.02±0.07),(0.87±0.09) and (0.96±0.12) × 10-3 mm2/s in moderate-to-severe HIE group.ADC values among the three groups had statistical difference (F=3.89,3.21,4.05,3.30,3.28,3.27,4.12,4.75and 4.72,all P＜0.05).ADC values of frontal lobe gray matter,frontal white matter,parietal gray matter,parietal white matter,putamen,posterior limb of the internal capsule and thalamus in mild HIE group were lower than those in control group (all P＜0.05).All of the ADC values of nine regions in moderate-to-severe HIE group were lower than those in control group (all P＜0.05).ADC value of frontal lobe gray matter,parietal gray matter,corona radiata,caudate nucleus,putamen,posterior limb of the internal capsule and thalamus in moderate-to-severe HIE group were lower than those in mild HIE group (all P＜0.05).Conclusion DWI and ADC values could reflect brain injury caused by HIE,and ADC values can be used to quantitatively analyze the degree of hypoxic-ischemic injury.

Background The alteration of dominance eye is associated with visual quality in patients with age-related cataract or after cataract-surgery.However,the study on the relationship of dominance eye shift with vision following cataract-surgery is lack.Objective This study was to observe the influence of age-related cataract and cataract surgery on ocular dominance in the elderly.Methods A serial cases-observational study was designed.Eighty-seven patients with age-related cataract were collected from December 2011 to April 2012 in Affiliated Eye Hospital of Wenzhou Medical University,and phacoemulsification combined with intraocular lens (IOL) implantation was performed in all the patients.The patients were grouped into binocular vision difference (best corrected distance vision) ≥2 lines group (42 patients) and ≤ 1 line group (45 patients) on the standard logarithmic visual acuity chart.The frequency and shift of dominant eye were determined by card-hole method or thumb method before operation and 1 day,1 week,1 month and 3 months after operation.The difference in the frequencies of dominant eye between before and after operation was analyzed with MecNmar test.Results The median of best corrected distance vision (LogMAR) was 0.40 (0.00-1.40) in preoperation and 0.00 (-0.08-0.30) in postoperation,with significant difference between them (Z=-9.481,P =0.000).In the binocular vision difference ≥ 2 lines group,the dominant eyes were 24 in the right eyes and 18 in the left eyes.The milder cataractous eyes were identified as dominant eyes in 33 (78.57％) patients and heavier cataractous eyes were determined as dominant eyes in 9 (21.43％) patients before operation.However,the right eye was evidenced as dominant eye in 31 patients and the left eye was in 11 patients after operation.In the 42 patients,dominant eye shifted from the left eyes to the right eyes in 10 patients and from the right eyes to the left eyes in 3 patients,and 4 patients presented an unstable change binocularly.In 45 patients of the binocular vision difference ≤ 1 line group,the dominant eyes were the right eyes in 27 patients and the left eyes in 18 eyes in preoperation ; while after operation,dominant eye altered form the left eyes to the right eyes in 3 patients and form the right eyes to the left eyes in 1 patient,and unstable change occurred in 5 patients.There were no significant differences in the frequency of dominant eyes between before and after operation both the two groups (group A:P =0.092 ; group B:P =0.727).Conclusions Age-related cataract impact on eye dominance.Dominance eye may occur alteration binocularly following cataract surgery,which is one of causes of visual discomfort.

Objective To learn the investigators′ satisfaction with CRCs and to identify the shortcomings with the CRC industry or institutional management for improvement. Methods A questionnaire survey was conducted among 120 clinical trial investigators at three tertiary general hospitals in January 2018. The questionnaire covered the basics, satisfaction with CRC, and comments of the investigator on other works of the CRC. The data acquired were subject to descriptive analysis, and the count data comparison method was Fisher precise test. Results The investigators were satisfied with CRCs in general. Specifically, their satisfaction with the " sense of responsibility" , " work hours" , and " command of GCP protocols"ranged 72.6% to 83.2% . That with " initiative" , " work stability" , and " rich clinical trial experience" fell below 60.0%. Affiliation of CRCs was correlated to "initiative"(P=0.007), and "command of clinical trial schemes and trial procedures" ( P =0.043), while investigators′ satisfaction with CRCs of uncertain affiliation fell significantly. Investigators′ experience was correlated to the " command of GCP protocols" of CRCs(P=0.035 ), as the more experienced the investigator, the less their satisfaction with the CRC. Conclusions Hospitals are expected to build a CRC standardized training system and hierarchical certification system; to standardize their CRC recruitment mechanism for overall management; to enhance their budgeting capability for sufficient CRC expenses, higher investigator efficiency and assured clinical trial quality.

Objective:To dynamically observe the effect of N-acetylserotonin (NAS) on the expression of tumor necrosis factor-α (TNF-α) protein in retina of retinal ischemia reperfusion injury (RIRI) rats, and to explore the mechanism.Methods:By using random number table method, 90 healthy male Sprague-Dawley rats were divided into sham operation group ( n=10), RIRI group ( n=40), and NAS group ( n=40). The right eye was as the experimental eye. In the RIRI group and NAS group, the anterior chamber high intraocular pressure method was used to establish the RIRI model. In the NAS group, 10 mg/kg NAS was injected intraperitoneally before modeling and 30 minutes after modeling. At 6, 12, 24, 72 h after modeling, hematoxylin-eosin staining was used to observe the pathological changes of the retina, and the retinal ganglion cells (RGC) were counted. Each group was detected by immunohistochemical staining and Western blot about the relative expression of TNF-α, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein in the rat retina. Oneway analysis of variance was used for differences between groups. The general linear regression method was used to analyze the correlation between the relative expression changes of TNF-α protein and the changes of Nrf2 and HO-1 protein expression after NAS intervention. Results:Optical microscope observation revealed that the retinal edema of rats in the RIRI group was observed at 6, 12, and 24 h after modeling; the thickness of the retina in the NAS group was significantly thinner than that in the RIRI group, and the difference was statistically significant ( F=9.645, 477.150, 2.432; P<0.01). At 6, 12, 24, and 72 h after modeling, the retinal RGC counts in the NAS group were significantly higher than those in the RIRI group, and the difference was statistically significant ( F=12.225, 12.848, 117.655, 306.394; P<0.05). The results of immunohistochemical staining and Western blot showed that 6 h after modeling, the relative expression of TNF-α protein in the retina of the RIRI group increased significantly compared with that in the sham operation group, reaching a higher level at 12 h, and decreased at 24 and 72 h. But all were significantly higher than the sham operation group, the difference was statistically significant (immunohistochemical staining: F=105.893, 1 356.076, 434.026, 337.351; P<0.01; Western blot: F=92.906, 534.948, 327.600, 385.324; P<0.01). At different time points after modeling, the relative expression of TNF-α protein in the retina of the NAS group was significantly lower than that of the RIRI group (immunohistochemical staining: F=15.408, 570.482, 21.070, 13.767; P<0.05; Western blot: F=12.618, 115.735, 13.176, 111.108; P<0.05), but still higher than the sham operation group (immunohistochemical staining: F=40.709, 151.032, 156.321, 216.035; P<0.01; Western blot: F=33.943, 79.729, 74.057, 64.488; P<0.01), the difference was statistically significant; 12 h after modeling, Nrf2 in the retina of the NAS group (immunohistochemical staining: F=51.122, P<0.05; Western blot: F=33.972, P<0.05), HO-1 (immunohistochemical staining: F=30.750, P<0.05; Western blot: F=18.283, P<0.05) protein relative expression was significantly higher than that of RIRI group, and the differences were statistically significant. The results of linear regression analysis showed that the difference in the number of TNF-α + cells in the RIRI group and the NAS group was negatively correlated with the difference in the number of Nrf2 + and HO-1 + cells ( r 2=0.923, 0.936; P<0.01). Conclusions:NAS can inhibit the expression of TNF-α protein in the retina of RIRI rats and reduce RIRI. The mechanism may be related to the Nrf2/HO-1 pathway.

Objective:To fabricate tAu@glutathione(GSH)@Gd nanoprobe for tumor angiogenesis bimodal (MR/CT) imaging, and evaluate its characteristics and potential for MR/CT imaging in vivo. Methods:The tAu@GSH@Gd nanoprobes were constructed by encapsulating Au and Gd atoms into the GSH shell with cyclic asparagine-glycine-arginine (cNGR) peptide conjugation. EMT-6 BALB/c mice subcutaneous transplantation tumor models were established ( n=30) and divided into blank control group (saline), control group (Au@GSH@Gd nanoparticles) and experimental group (tAu@GSH@Gd nanoprobes) ( n=10 in each group). In vivo MR/CT imaging and distribution study were performed at different time points after tail intravenously injection. Relative MR signal value and relative CT value of tumor site and main organs in mice were used to evaluate MR/CT imaging property and biological distribution. After that, tumor tissues were collected for silver staining to study the accumulation of Au@GSH@Gd nanoparticles and tAu@GSH@Gd nanoprobes. Independent-sample t test was used for data analysis. Results:The tAu@GSH@Gd nanoprobes were (6.40±0.22) nm with high T 1 relaxation efficiency ((36.91±0.07) mmol·L -1·s -1). MR/CT imaging of tAu@GSH@Gd nanoprobes showed good performance in vitro. In vivo MR/CT imaging demonstrated MR/CT imaging of tumor was significantly enhanced by tAu@GSH@Gd nanoprobes after 2 h post injection. The strongest enhancement was observed at 24 h, with an increased relative MR signal value from 1.04±0.12 (before injection) to 1.84±0.26 ( t=12.61, P=0.006), and increased relative CT value from 1.01±0.04 (before injection) to 1.95±0.05 ( t=15.34, P=0.004). The highest MR/CT effect in control group appeared at 16 h, with the relative MR signal value of 1.50±0.06 and the relative CT value of 1.53±0.10, which were significantly lower than those in experimental group (1.84±0.26 and 1.95±0.05; t values: 5.35 and 16.46, both P<0.05). Distribution in normal tissues showed that most of tAu@GSH@Gd nanoprobes were metabolized through the kidneys. Tissue silver staining experiment verified the tumor angiogenesis targeting effect. Conclusion:The tAu@GSH@Gd nanoprobes exhibit favorable tumor angiogenesis target MR/CT imaging ability, providing a new design concept and basis for assessing tumor angiogenesis.

Objective To investgate the application value of low-dose CT scanning in right adrenal vein imaging.Methods A total of 124 patients were enrolled in the study who were suspected as primary aldosteronism and requiring a contrast enhanced CT examination on adrenal glands.Four patients were excluded according to the exclusion criteria,so that the rest 120 patients were divided equally into three groups.Group A was a control group with conventional radiation dose using tube voltage of 120 kV and automatic mA.It was divided into A1,A2 and A3 groups according to arterial phase,portal venous phase and parenchymal phase.Group B was a experimental group with conventional tube voltage of 120 kV and automatic mA,which was divided into B1,B2 and n3 groups according to arterial phase,late arterial phase and portal venous phase.Group C was a low-dose experimental group with a tube voltage of 100 kV and a tube current of 150 mA only in the second phase,the remaining scanning parameters and method were the same as that of group B.The subjective scores of the images of groups A,B and C were statistically analyzed,and the CT values of the right adrenal vein(RAV),the right adrenal gland(RAG),and the fat of anterior abdominal wall at different scan phases were measured.The dose length products (DLP) were recorded and the signal-to-noise ratios (SNR),contrast-to-noise ratios (CNR),effective doses (E) of the three groups were calculated and compared.Results The subjective scores of the two observers were consistent (Kappa value =0.63);the subjective scores of the B2 images were statistically significant (H =7.18,P＜0.05).Difference of subjective scores between B2 and A2was statistically significant (t=-18.03,P＜0.05).The CT values of RAV,SNR,and CNR of the B2 group were higher than those of the A2 group (t=36.99,6.92,9.02,P＜0.05).The radiation dose comparison showed that the effective dose (E) was 45.52％ lower in the low-dose group than the conventional dose group with the statistically significant difference(t =12.19,P＜0.05).Conclusions Using MDCT scanning technique with lower tube voltage and lower tube current of 100 kV-150 mA,the detection rate of right adrenal vein can reach 95％ in the late arterial phase,and the effective dose can be reduced about 45.52％ on the basis of ensuring image quality.

Objective To prepare polyethylene glycol/cyclic asparagines-glycine-arginine functionalized gold nanoparticles (GNPs-PEG@cNGR) and evaluate their effectiveness in CT imaging of breast cancer angiogenesis.Methods The GNPs were synthesized by one-step reduction of chloroauric acid by sodium citrate.The thiolated PEG and cysteine-modified cNGR were coupled to the surface of GNPs through Au-S bonds,respectively.The GNPs-PEG@cNGR was characterized by transmission electron microscopy,Zeta potential/hydration particle size analyzer,and Fourier transform infrared spectrometer.The uptake and CT imaging effect of GNPs-PEG@cNGR were assessed by human umbilical vein endothelial cells (HUVEC) and human hepatoma cells (HepG2) positively expressed for aminopeptidase N (APN/CD 13).The in vivo CT imaging effects on tumor angiogenesis and biocompatibility in mice of GNPs-PEG@cNGR were studied by BALB/c mouse model of 4T1 breast cancer.Results A specific CT molecular probe,i.e.GNPs-PEG@cNGR,was successfully constructed,which can target angiogenesis.The probe was spherical,with a hydration particle size of (35.7± 1.0) nm and a Zeta potential of (-13.54± 1.12) mV,and had good stability and biocompatibility.The GNPs-PEG@cNGR has good CT imaging results and can specifically target CD13-positive HUVEC and HepG2 cells.The CT imaging results in 4T1 breast cancer mice indicated that GNPs-PEG@cNGR could be specifically enriched in the tumor tissue after injection.The CT value of tumors in GNPs-PEG@cNGRz group was higher than that of GNPs-PEG group,and the difference was statistically significant (P＜0.05).Conclusions GNPs-PEG@cNGR can specifically target CD13 positive cells and can be used as a CT contrast agent for imaging tumor angiogenesis.

Objective To investigate the difference of the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein between primary lesions of breast cancer and its synchronous ipsilateral lymph node metastasis,as well as its clinical implications.Methods Retrospectively analyze invasive breast cancer patients treated in Peking University First Hospital from January 2012 to May 2016.The IHC expressions of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein in both the primary and lymph node metastatic lesions are compared and analyzed statistically.The count data were represented as n(％),and comparsion between groups were evaluated using the McNemar test.Results One hundred and fifty-six patients were included,of which on 2 cases (1.3％),estrogen receptor status of primary lesions is different from that of lymph node metastases(P =0.500);on 10 cases (6.4％),progesterone receptor status of primary lesions is different from that of lymph node metastases (P =0.344);on 28 cases (18.0％),Ki-67 protein status of primary lesions is different from that of lymph node metastases (P =0.000 18);on 3 cases (1.9％),human epidermal growth factor receptor 2 status of primary lesions is different from that of lymph node metastases (P =1.000).Conclusion There may be difference between primary lesions and lymph node metastases in the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein,which can provide a reference for individualized treatment of breast cancer patients.