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The development of multifunctional nanocontrast agents with high sensitivity, high specificity, and low toxicity so that they can precisely localize tumors and reflect tumor biological information in real time is the core of promoting the development of tumor molecular imaging technology and realizing early and precise tumor diagnosis. Polydopamine (PDA) nanomaterials are bionanomaterials with a structure extremely similar to that of natural melanin. They can be easily fabricated and functionalized, and can achieve controlled assembly of functional molecules such as contrast components and targeting ligands via metal coordination, π-π stacking, electrostatic adsorption, and other methods. They have good biocompatibility and biodegradability, show great potential for clinical translation, and have been widely used in molecular imaging of tumors. In this review paper, the preclinical studies of PDA nanoparticles are reviewed as well as the synthesis methods, functionalized modification, and assembly strategies of PDA nanoparticles and their applications in tumor molecular imaging. The development trends of PDA are also presented to promote their application in the field of tumor molecular imaging.
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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.
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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.
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OBJECTIVE：To provide reference for constructing and improving the pharmacovigilance signal management sys - tem in China by comparing signal management system among the European Union （EU），the United States （U. S. ）and Japan. METHODS：Literature analysis method was used to systematically compare the similarities and differences on definitions ，sources， detection methods and management process of pharmacovigilance signals among EU ，U. S. and Japan. Some suggestions were put forward for pharmacovigilance management in China. RESULTS & CONCLUSIONS ：Regulatory authorities of the EU ，U. S. and Japan did not have a uniform definition on signals ；EU drug administration adopted the definition of the eighth working group of Council for International Organizations of Medical Sciences ，FDA adopted its own definition ，while the Japanese regulatory agency had no clear definition. Currently ，post-marketing surveillance still relied mainly on spontaneous reporting systems ；EU，U. S. and Japan had carried out the signal detection based on the spontaneous reporting system ；EU mainly adopted the proportional reporting ratio method ，U. S. mainly adopts the multiple gamma Poisson Shrinker ，and Japan mainly adopted the reporting ratio method. EU had special guidelines for signal management process ，while the U. S. and Japan did not. It is recommended to accelerate the deve- lopment of the legal and regulatory framework on pharmacovigilance in China ，draw up guidelines on pharmacovigilance practices ， strengthen the active ADR surveillance and promote the application of data mining techniques in signal detection field ，for accelerat - ing the standardization and internationalization of China ’s pharmacovigilance work.
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Tumor neovascularization plays an important role in the occurrence, development and metastasis of cancer. Non-invasive quantification and detection of tumor neovascularization is crucial for early diagnosis and prognosis assessment of cancer. Targeted molecular imaging has arisen in vascular targeting imaging and precise treatment based on the molecular characteristics of neovascularization. Aminopeptidase N (APN, or CD13) is a multifunctional membrane-bound exopeptidase that is overexpressed in neovascular endothelial cells and some tumor cells but rarely expressed in normal blood vessels, which makes it a potential target for tumor neovascularization imaging and anti-angiogenic therapy. This review summarizes the application progress and the future development trend of target molecular imaging and precise treatment based on CD13.
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Objective To analyze the related risk factors of choledocholithiasis recurrence after endoscopic sphecterotomy (EST) and choledocholithotomy.Methods A retrospective analysis was made on 734 patients who underwent EST + endoscopic papillary balloon dilation and stones restraction (EPBD) operation with preoperative MRCP imaging and follow-up data from Jan 2012 to Jan 2015.The distribution of MRCP-related signs in patients with and without recurrence of stones was statistically analyzed.Results Preoperative or intraoperative cholecystectomy,peripapillary diverticulum,multiple choledocholithiasis and common bile duct angle were independent risk factors for recurrence of cholelithiasis.Conclusion Small incision EST + EPBD may preserve the function of Oddi sphincter and minimize the trauma to the patient,but there are still some preoperative factors that may affect the recurrence of stones.
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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.
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Objective To evaluate the clinical value of CT urography (CTU) in quantitative analysis of single?kidney renal glomerular filtration rate (GFR) in patients with renal tumor and hydronephrosis.Methods A total of 49 patients with renal tumor or hydronephrosis from January 2018 to September 2018 in the Second Hospital of Tianjin Medical University were prospectively collected. In all cases, the CT urography and 99mTc?DTPA renal dynamic imaging data and related clinical data were collected. All patients were divided into two groups: the experimental group (39 patients with a total of 78 kidneys) and the validation group (10 patients with a total of 20 kidneys). According to the presence or absence of renal diseases, the kidneys of the experimental group and the validation group were further divided into four groups, namely, the single kidney group, the tumor group, the stagnant water group and the healthy group. The CT urography protocol consisted of noncontrast, arterial phase, nephrographic, and excretory phase imaging. The total renal GFR was determined by CT measurement of renal clearance of contrast media (CM), and the total CT?GFR was then split into single?kidney CT?GFR by a left and right kidney proportionality factor. Differences between CT?GFR and SPECT?GFR measurements in each group of the experimental group was compared by paired?sample t test. Correlations between CT?GFR and SPECT?GFR in the experimental group and their correlations with RPV was analyzed by Pearson method. The Bland?Altman mapping method was used to evaluate the consistency between CT?GFR and SPECT?GFR in the experimental group. Results Paired difference between single?kidney CT?GFR (48.76 ± 18.50) ml·min-1·1.73 m-2 and single?kidney SPECT?GFR (45.68±17.95) ml·min-1·1.73 m-2 in the experimental group, P<0.05, demonstrating 6.8% systemic overestimation. A good correlation(r=0.80, P<0.01) and consistency (± 22.50 ml·min-1·1.73 m-2, ± 49.2% measurement deviations) was revealed between both measurements. There were positive correlations between CT?GFR and SPECT?GFR in the renal tumor group, hydronephrosis group, and healthy kidney group (r=0.67, 0.92, 0.80; P<0.01) respectively, and with good agreement (95% CI measurement deviation<30 ml·min-1·1.73 m-2). In all validation groups, there was no statistical difference between the estimated and true values of the Gates?GFR (all P>0.05). Pearson Correlation analysis showed that the correlations between CT?GFR and RPV in all experimental groups were better than the correlation between Gates?GFR and RPV (P<0.05). Conclusions This study demonstrated the feasibility of using CT urography to measure single?kidney GFR, verifying its application value in diseases such as kidney tumors and obstructive hydronephrosis, and proved that the proposed single?kidney CT?GFR correlates better than the SPECT?GFR with RPV.
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Objective@#To explore the dynamic variation trend of bronchial wall thickness (BWT) in severely burned patients combined with inhalation injury, and to determine the value of BWT to prognosis of patients.@*Methods@#Forty-three severely burned patients with inhalation injury hospitalized in Intensive Burn Department of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital) from July to November 2016, conforming to the study criteria, were divided into survival group (n=27) and death group (n=16) according to the prognosis of patients within 14 days after admission. All patients underwent fiberoptic bronchoscopy and inhalation injury rating based on abbreviated injury scale at admission. High resolution CT examination was performed in patients of two groups at admission and 24 h post admission, 3, 7, and 14 d post admission to measure the BWT of right superior lobar bronchus trunk opening. Receiver operating characteristic curves of rating of inhalation damage at admission and BWT at admission were drawn to evaluate the predictive value for death of 43 patients. Data were processed with chi-square test, independent sample t test, Wilcoxon rank sum test, analysis of variance for repeated measurement and least-significant difference-t test.@*Results@#(1) The numbers of patients rated as 0, 1, 2, 3, and 4 grade for inhalation injury in survival group and death group were 0, 19, 6, 2, and 0, and 0, 2, 7, 7, and 0, respectively. There were statistically significant differences between the two groups (Z=-3.79, P<0.01). (2) BWT of patients in death group at admission and 24 h post admission, 3, 7, and 14 d post admission was respectively (2.72±0.26), (3.18±0.22), (2.98±0.18), (2.29±0.17), and (1.45±0.21) mm, which was significantly larger than (2.24±0.15), (2.49±0.15), (1.51±0.17), (1.04±0.16), and (1.01±0.13) mm in survival group (t=7.55, 12.14, 27.11, 19.99, 7.11, P<0.01). BWT of patients in survival group and death group at 24 h post admission, 3, 7, and 14 d post admission showed statistically significant difference when compared with that at admission within the corresponding group (t=5.97, 16.63, 28.21, 38.57, 5.34, 3.31, 4.39, 6.48, P<0.01). BWT of patients in survival group and death group on 3, 7, and 14 d post admission was significantly smaller than that at 24 h post admission within the corresponding group (t=22.27, 34.02, 45.03, 2.77, 10.53, 10.59, P<0.01). BWT of patients in survival group and death group on 7 and 14 d post admission was significantly smaller than that on 3 d post admission within the corresponding group (t=10.49, 18.26, 9.57, 11.44, P<0.01). BWT of patients in survival group and death group on 14 d post admission was significantly smaller than that on 7 d post admission within the corresponding group (t=6.97, 6.15, P<0.01). (3) The total areas under ROC curves of inhalation injury rating at admission and BWT at admission for predicting death of 43 patients were 0.880 and 0.956, respectively (with 95% confidence intervals 0.768-0.991, 0.882-1.000, P<0.05). Grade 1.5 and 2.75 mm were respectively chosen as the optimal threshold values of inhalation injury rating at admission and BWT at admission, with sensitivity of 87.50%, 83.33% and specificity of 77.78%, 96.00%, respectively.@*Conclusions@#The BWT of survived and dead patients with severe burn and inhalation injury increases significantly post burn, while the BWT of survived patients restores to normal level faster. BWT can be used to assess the severity of inhalation injury and to predict death in severely burned patients combined with inhalation injury.
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Objective To prepare pH-responsive osmotic nanocarriers (pMPPs),observe their distribution in the genital tract mucosa in mice,and evaluate their radiosensitizing effects in tumor cells.Methods Amphiphilic polymers containing pH-sensitive hydrazone bonds were synthesized and pMPPs were prepared by ultrasonic emulsification.At the same time,the hydrophobic polymer polylactic acid-glycolic acid copolymer (PLGA) and the amphiphilic polymer PLGA-polyethylene glycol without hydrazine bond were selected,and the mucoadhesive nanoparticles(MPs) and mucus-penetrating particles (MPPs) were prepared in the same way.Fluorescence microscopy was used to observe the distribution of three kinds of nanocarriers labeled with fluorescent dye Cy5.5 in the genital tract mucosa.The toxicity of nanocarriers to human cervical cancer cell line HeLa was tested by thiazolyl blue assay.The amphiphilic polymer containing pH-sensitive hydrazone bond was combined with oil-soluble gold nanoparticles to form a multi-encapsulated nanocarrier,and its radiotherapy sensitization effect in HeLa cells was evaluated by thiazole blue assay.Results The pMPPs were successfully prepared with relatively uniform particle size and good dispersion.Fluorescence microscopy showed that pMPPs not only had good mucus permeability,but also could improve the endocytosis efficiency of the nanocarriers in reproductive tract mucosa.The results of thiazolyl blue test showed that when the concentration of the carrier reached to 0.80 mg/ml,the survival rate of HeLa cells in the pMPPs group was higher than 90％ which was higher than that in the MPs and the MPPs groups,indicating that pMPPs had good biosafety.The HeLa cell survival rate of the CMNa group (0.80 mg/ml) was higher than that of the multi-package nanocarrier group under different doses of X-ray irradiation (4 Gy:82.90％ vs.61.79％;8 Gy:64.75 ％ vs.42.36％).This result indicated that compared with the CMNa,a commonly used clinical radiotherapy sensitizer,the multi-encapsulated nanocarriers can more effectively enhance the sensitivity of tumor cells to radiation therapy,thereby improving the lethality of radiation therapy on tumor cells.Conclusion This study solved the conflict between mucus permeation and endocytosis design of nanocarriers in mucosal tissue application,and provided new insight for the treatment of mucosal tissue diseases.
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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.
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Objective To explore the value of dual-source dual-energy CT (DSDE-CT) in differentiating extravasation of iodine contrast agents from secondary hemorrhage after revascularization in acute ischemic stroke. Methods 46 acute ischemic stroke patients following intra-arterial thrombolysis were examined with DSDE-CT within 2 hours after the procedure. Simultaneous imaging at 80 kV/392 mA and 140 kV/196 mA was employed, and then mixed images, virtual unenhanced non-contrast images and iodine overlay maps were calculated. Mixed images alone, as conventional CT, and DUDE-CT interpretations were assessed separately by two radiologists and compared with follow-up CT. Results 6 of 34 patients were negative cases proven by CT without high density, and another 28 cases were proven positive cases with 3 cases of cerebral hemorrhage, 21 cases of contrast agent extravasation, and the remaining 4 cases of combined cerebral hemorrhage and contrast agent extravasation. The sensibility, specificity, positive predictive value, negative predictive value and accuracy of mixed imaging alone in diagnosing hemorrhage was 66.67%, 100%, 1005, 96.15% and 96.43%, while the sensibility, specificity, positive predictive value, negative predictive value and accuracy of hemorrhage with DUDE-CT was 100%, 96%, 75%, 100% and 96.43% . The diagnostic accuracy of superimposed fusion images for intracranial hemorrhage, extravasation of contrast agent and hemorrhage with extravasation of contrast agent was relatively high, and the difference was statistically significant (P < 0.05). The diagnostic accuracy of superimposed fusion images consistent with clinical follow-up was significantly higher (Kappa=0.815),as compared with that of mixed imaging alone (Kappa=0.0.564). Conclusion DUDE-CT has great value in differentiating hemorrhage from iodinated contrast after intra-arterial thrombolysis in acute ischemic stroke.
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OBJECTIVE:To establish a method for the concentration determination of gabapentin (GBP) in human plasma.METHODS:After precipitated by methanol,using sulfamethoxazole as intemal standard,LC-MS/MS method was adopted.The determination was performed on Diamonsil C18 column with mobile phase consisted of water (containing 0.05％ formic acid)-methanol using a gradient elution program at the flow rate of 1 mL/min.The column temperature was 30 ℃,and sample size was 20 μL.The ESI was equipped and quantitative analysis was operated in positive ion and MRM mode.The mass transition ion-pairs were followed as m/z 172.0→154.1(GBP) and m/z 279.0→124.0 (internal standard).RESULTS:The linear range of GBP was 13.4-10 720.4 ng/mL (r=0.992 3,n=5).The limit of quantitation was 13.4 ng/mL,and the minimum detection limit was 4.0 ng/mL.RSDs of inter-day and intra-day were all lower than 10％.Relative errors ranged-4.93％-5.10％.The recoveries ranged 86.2％-90.3％ (RSD＜5％,n=6),and matrix effects ranged 87.6％-92.1％.The plasma concentration of GBP in 10 epileptic patients ranged 2 075.19-4 078.87 ng/mL (n=20).CONCLUSIONS:The method is proved to be sensitive,specific,practical and suitable for plasma concentration monitoring and pharmacokinetic study of GBP in epileptic patients.
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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.
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Objective To investigate the short?term functional connectivity (FC) changes of default mode network (DMN) after liver transplantation (LT) by using seed?based functional connectivity analysis of resting?state functional MRI (rs?fMRI). Methods Eighteen cirrhotic patients as transplant candidates and 20 healthy controls were included in this study. All the patients underwent rs?fMRI examination before and one month after LT. The data were analyzed using DPARSF and REST software. Seed?based functional connectivity analysis was used to isolate the DMN. The posterior cingulate cortex (PCC) was chosen as seed region for the DMN map. Maps of the DMN were compared among the groups. Values of Z reflecting the functional connectivity of 3 groups were obtained. Two?sample t?test was performed to explore the DMN difference between cirrhotic patients and controls, and we used paired t tests to examine for any differences in functional connectivity before and after LT. Pearson correlation analysis was performed to explore the relationship between the changes of functional connectivity with that of clinical indexes and neuropsychological test scores pre?and post?LT. Results Typically spatial distributions of the DMN were found in all the groups. According to paired t test, post?LT patients showed increased FC in left medial prefrontal cortex (t=3.31, P<0.05), while decreased FC in left precuneus and left lateral temporal cortex (t=-3.37,-4.53,respectively, both P<0.05). Compared to healthy controls, pre?LT patients showed decreased FC in the right precuneus, bilateral medial prefrontal cortex, bilateral inferior parietal cortex, and bilateral lateral temporal cortex(t=-4.32—3.00, all P<0.05), and post?LT patients showed decreased FC in right precuneus, left posterior cingulate cortex, bilateral inferior parietal cortex, and bilateral lateral temporal cortex(t=-4.33—2.99,all P<0.05). Pearson correlation analysis revealed positively correlation between the changes of functional connectivity in left medial prefrontal cortex with that of DST (r=0.543, P=0.02). Conclusions This study found that the DMN FC of post?LT patients still lower than that of healthy controls one month after LT. The left medial prefrontal cortex was the first brain region that showed increased FC, while the FC of some regions continued to decrease, suggesting that brain function reorganization can continue after LT. Rs?fMRI can be used to observe the DMN changes in post?LT patients.
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OBJECTIVE:To establish a method for the content determination of Esomeprazole sodium for injection. METH-ODS:UPLC-MS/MS was performed. The column of ZORBAX Eclipse Plus C18 with 0.1% formic acid-methanol(73∶27,V/V)at a flow rate of 0.3 ml/min,column temperature was 35℃,analysis time was 5 min,injection volume was 2μl;ionization mode was positive ion mode,ion source temperature was 150 ℃,capillary voltage was 3.0 kV,cone voltage was 50 V,cone flow was 150 L/Hr,desolvation temperature was 450 ℃,desolvation gas flow was 900 L/Hr,nebuliser pressure was 7.0 Bar,parent ion scan range was 100-800 mz/mz,working mode was multiple reaction monitoring mode. RESULTS:The linear range of esomeprazole was 0.2-20.0 ng/ml(r=0.999 7);the limit of quantitation was 50 pg/ml;RSDs of precision,stability and reproducibility tests were lower than 2%;recovery was 99.93%-100.05%(RSD=0.1%,n=9). CONCLUSIONS:The method is simple and accurate,and can be used for content determination of Esomeprazole sodium for injection.
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Objective To evaluate the influence of the CT enterography (CTE) in different scan phases of small intesti?nal wall and arteriovenous vessels, and to confirm the diagnostic efficiency thereof. Methods A total of 286 patients under?went CTE were collected, and their CT image of three scan phases, including 20 s, 40 s and 60 s after injection, were record?ed. Values of reinforcement of the intestinal wall and arteriovenous enhancing degree in all phases were collected. A statisti?cal analysis was used to confirm the best phase for showing the structure. The diagnostic efficiency of the best phase of CT image was evaluated for the clinical diagnosis of small intestine and vascular lesions. Results (1) The CT value of the small intestinal wall in the intestinal phase was significantly higher than other two phases (Pintestinal phase, and there is no statistical difference between the intestinal phase and oth?er two phases. The result of CT value of ileum vein showed that intestinal phase>portal phase>arterial phase (P<0.05). (3) The sensitivity was 95.8%, the specificity was 94.9%, the accuracy was 95.1%, the positive predictive value was 79.3%and the negative predictive value was 99.1%using CT image of intestinal period for diagnosing small intestinal diseases. (4) The intestinal period showed small intestinal lesions and confirmed by pathology including 22 cases of small intestinal lympho?ma, 10 cases of stromal tumor, 1 case adenoma, cavernous 3 cases hemangioma and 8 cases of Crohn's disease. The diagno?sis of hemangioma should be combined with arterial phase. Conclusion Small intestinal wall and blood vessels have better display performance in the intestinal phase of multiphase CT enterography, using the arterial phase and intestinal phase scan?ning, we can make an accurate diagnosis for the majority of small intestinal diseases.
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OBJECTIVE:To provide the reference for verifying and improving the usage criteria and guidelines of compound oral contraceptives(COCs)in China. METHODS:The usage criteria and guidelines of COCs were introduced and compared issued by WHO,US and European Union(EU). RESULTS&CONCLUSIONS:WHO has established 4 standards and guidelines for COCs, i.e. Medical Eligibilitu Criteria for Contraceptive Use(MEC),Selected Practice Recommendations for Contraceptive Use(SPR), Decision-making Tool for Family Planning Clients and Providers,Family Planning:A Global Handbook for Providers. According to the specific circumstances of the user,MEC has been divided into 4 levels according to the situation of users,i.e. suitable for use,use cautiously,relative contraindication,absolute contraindication. SPR mainly describes the specific issues of how to use vari-ous contraception methods safely and effectively. The reading card mode for Decision-making Tool for Family Planning Clients and Providers can query specific methods and steps of contraceptive informed choice fast. Family Planning:A Global Handbook for Providers can provide practical guide for the family planning service providers in the first line. On the basis of WHO MEC and SPR,some projects are modified and added in the US MEC and SPR,including the classification of breast feeding,the risk grade of DVT/PE recurrence,etc. EU have formulated COCs criteria and guidelines earlier than WHO and US;the key points and specif-ic varieties of COCs are prompted and updated based on the latest evidence- based medicine,including a new assessment of the risk of thrombosis after using the COCs,the special safety tips for the use of Diane 35? and its generics. Concerning the optimal ev-idences of current COCs usage of WHO,US and EU,combined with domestic situation,our country may provide the clear and up-to-date usage criteria and guidelines of COCs for its users and medical staff.
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Objective To explore the effects of different doses of contrast agent (CA) on types of time-signal intensity curves (TICs) and semi-quantitative parameters after dynamic contrast-enhanced MRI (DCE-MRI) on Walker 256 murine breast tumor model.Methods A total of 12 rats burdened Walker256 breast cancer models were established and divided into 3 groups randomly, 4 in each group.Routine MR and DCE-MRI scans of the rats using Bruker Pharmascan 7T MR scanner were performed.Doses for the 3 groups were 0.2, 0.3, and 0.5 mmol/kg, respectively.MR data, TICs types and semi-quantitative parameters from each different dose group were statistically studied and compared to observe the differences.Results Tumors were enhanced significantly after injection.The types of TICs in all tumors were the Ⅲ pattern which was not influenced by CA doses.Semi-quantitative parameters of first enhancement (Efirst), maximal enhancement (Emax), washout enhancement (Ewash), and signal enhancement ratio (SER) showed statistical differences among the three dose groups (P＜0.05).Semi-quantitative parameters of time to peak (Tpeak) and washout velocity (Vwash) showed no statistical differences among the three dose groups (P＞0.05).Mean signal intensity of each group was highly negatively linear correlated with scan times after the peak (r=-0.972, P=0.000;r=-0.971, P=0.000;r=-0.989, P=0.000).The washout slope (slopewash) showed no statistical differences among the three groups (P＞0.05).Conclusions Injection doses of CA didn't change the TIC type, Tpeak, Vwash, and Slopewash.These parameters are comparable among different medical centers and can be considered as prior parameters to monitor the efficacy of neoadjuvant chemotherapy.
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<p><b>OBJECTIVE</b>To explore the possibility of predicting the histopathological types of small renal cell carcinoma (RCC) by analyzing the different ways of enhancement with multiphasic multidetector computed tomography (MDCT) of small renal cell carcinomas (diameter≤4 cm).</p><p><b>METHODS</b>CT images of 93 cases, diagnosed as RCC by pathology, were analyzed retrospectively, including 70 clear cell renal cell carcinoma (CCRCC), 13 papillary renal cell carcinoma (PRCC) and 10 chromophobe renal cell carcinoma (CRCC). All of the cases were examined by multiphasic multidetector CT scanning.</p><p><b>RESULTS</b>In plain scans, 46 CCRCCs were homogeneous, 21 CCRCCs were heterogeneous with low-density area and 3 of them had calcification. CCRCCs were enhanced in contrast scan with a presence of "wash in and wash out" enhancement in general. 11 PRCCs were homogeneous and 2 PRCCs had calcification. Slight-homogeneous enhancement and "delayed enhancement" were present in the PRCCs. Six CRCCs were homogeneous and 2 were calcified, 2 CRCCs were heterogeneous with low-density area. The CRCCs presented as slight or moderate enhancement and 5 CRCCs as homogeneous enhancement, while one CRCC was "spoke-wheel-like enhancement", with a trend of "delayed enhancement". Statistically significant differences were revealed among the actual enhanced CT values, the ratio of enhanced CT value to aorta CT value in the corticomedullary phase, nephrographic phase and excretory phase between the CCRCCs and non-CCRCCs (P<0.001). The analysis of receiver operating characteristic curves (ROC) revealed that when the actual enhanced CT value of tumors in CMP larger than 84.2 HU, the ratio of actual enhanced CT value to aorta CT value at the same phase in CMP larger than 0.315 were used as criteria to diagnose CCRCCs and excluded non-CCRCCs, the diagnostic value was best.</p><p><b>CONCLUSIONS</b>MDCT is of an important significance in the diagnosis and differential diagnosis of small CCRCCs and non-CCRCCs.</p>