Despite tre mendous research efforts have been devoted to the analysis of nanoparticles (NPs)biohazard,the potential mechanism for nanotoxicity has not yet been syste mati-cal y elucidated.This review intends to point out the confusions about nanotoxicity in the field and tries to look into the mecha-nism from a new perspective.Currently,there are three puzzles:① no relationship between dose and toxicity could be observed in nanotoxicity;②there is a theory for the″size effects″,however, it cannot explain some cases contrary to the doctrine;③ NPs made of different materials with various sizes could have the same toxic effects through sti mulating oxidative stress.In fact, human body is co mposed of various biological molecules,and the biological function of a living syste m is reflected by the inter-actions and conversions of those molecules.NPs,on the other hand,are the invader of human body which has no ability to transport or convert or digest the foreigner.Thus,NPs could cause celldamage due to the physical blockage of micro-circula-tion,celldestruction due to membrane rando m insertion,and celldysfunction due to physical contacting with big biological mole-cules.The physical damages caused by various NPs could be divided into three categories:adhesion lesion,card inlay and puncture.Above al ,by analyzing wide spectrum of NPs varying in co mposition,shape and size,the author draws a conclusion that physical damage is the origin of nanotoxicity.

Objective To evaluate the change of myasthenia gravis(MG) during radiotherapy for patients with malignant thymomas.Methods Forty-five with malignant thymomas patients with were analyzed.The median total dose was DT54.2?Gy in 1.8-2.0?Gy /fraction,5 days a week.Anti-cholinesterase,such as pyridostigmine was used to control the MG symptoms.Results Forty-five patients completed radiotherapy on schedule except one from whom the treatment was was with drawn because of respiratory muscle involvement.Among these 44 patients,myasthenic symptom was relieved in 4 to various degrees,4 progressed,34 no change and 2 developed cholinergic crisis.Myasthenic symptom was not changed in one patient for whom radiotherapy had been standed before operation nor during the course of postoperative radiotherapy.Conclusions A course of radiotherapy of DT54.2?Gy,on fractionation of DT1.8-2.0?Gy modal would not aggravate myasthenia.However,proper use of anti-cholinesterase,careful observation and timely drug-adjustment are necessary.

Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.

Objective To develop an MR optical dual-modality probe targeting angiogenesis of gastric cancer and to study its physical characteristics , in vitro cytotoxicity and magnetic effects of different pulse sequences on 3 T clinical MR scanner.Methods We conjugated GX1-Cy5.5, a novel gastric cancer neo-vasculature targeted peptide labeled with Cy 5.5, to the surface functionalized magnetic nanoparticles according to different molecular weights (1∶100, 1∶500),resulting in dual-modality probe DPs100 and DPs500 (named DPs).The hydrodynamic size and zeta potential of DPs and DPs 500 were analyzed by nano-ZS.The human umbilical vein endothelial cells (HUVECs) and BGC-823 cells were treated with DPs for 24 h, and methyl thiazol tetrazolium ( MTT) method was used to detect the survival rate of cells.DPs with different concentrations were scanned on different MR sequences , and then the relative signal intensity was observed.The absorbance of HUVECs and BGC823 cells treated with DPs of different concentration (0.00, 1.25, 2.50, 15.00, 50.00, 100.00 and 150.00 μg/ml) were compared with single factor analysis of variance.Relative signal intensity of different MR sequences was compared using a paired Wilcoxon signed-rank test.Results The dual-modality probe targeting angiogenesis of gastric cancer was successfully constructed.The hydrodynamic size of iron oxide nanoparticles , DPs100 and DPs500 was (35.23 ±0.07), (39.49 ±0.16) and (40.43 ±1.70) nm and the Zeta potential was (0.31 ±0.20), ( -4.15 ±0.79) and ( -10.51 ± 2.37) mV.The coupled rates of DPs 100 and DPs500 with polypeptide were 92%and 94% respectively.The absorbance of HUVECs and BGC823 cells treated with DPs of different concentrations were 0.76 ±0.04, 0.80 ±0.03, 0.79 ±0.05, 0.75 ±0.06, 0.74 ±0.05, 0.77 ±0.01,0.71 ±0.04 and 0.38 ±0.04, 0.43 ±0.04, 0.41 ±0.03, 0.43 ±0.07, 0.44 ±0.04, 0.41 ±0.07 and 0.40 ±0.04, there was no statistical significance ( F=0.94, 0.51;P>0.05).The signal intensity increased first and then decreased following the increasing concentrations of DPs on T 1WI,especially on FSPGR T1WI (Z =-3.294,P <0.05), while the signal intensity decreased on T2WI or T2*WI.There was no significant differences in signal intensity on FSE T2 WI and SSFSE T2*WI with iron concentration >10μg/ml( Z=-7.110,P>0.05).With iron concentration≤10 μg/ml,the signal intensity on SSFSE T 2*WI was significantly decreased compared to FSE T2 WI ( Z =-2.023, P <0.05 ) .Conclusions DPs may be potential dual-modal probes for characterization of tumor angiogenesis by MR and optical imaging noninvasively , without causing significant effects on the cell activity in vitro , and SSFSE T2*WI may be the most sensitive sequence for DPs evaluation on MR.

Objective To observe the clinical effect of Chuanxiong-Chatiao San in treatment hemicrania. Methods All patients were randomly recruited into a control group (75cases) and a treatment group (78 cases). The control group was treated with Gastrodin injection, Ligustrazine injection and Mailuoning injection; on this basis, the treatment group was treated with Chuanxiong-Chatiao powder. Both groups were treated for 14 days with a 7 days interval. Results The excellent rate and effective rate were 91.03% and 96.08% in the treatment group respectively; and 70.66% and 94.67% in the control group respectively. The difference between the two groups was significant (χ2= 12.7143,P<0.01) . Conclusion Chuanxiong-Chatiao powder combined with western medicine is effective in treating hemicrania.

Objective To compare the planning systems of the simplified manual intensity modulated (SMIM) irradiation and standard tangential (ST) irradiation,in order to explore the application of SMIM technique in clinic.Methods In 64 cases of breast cancers after breast conserving surgery,each underwent both SMIM and ST planning systems.SMIM planning was designed by copying additional fields for shielding the high dose areas from internal or lateral tangential field.The high dose areas were reduced by adjusting the size of the additional field and open tangential field.To optimize the SMIM planning,3 high dose areas (＞ 103% ,＞ 105% and ＞ 107%) were shielded and 3 protocols carried out.The wedges were also optimized in ST plan.The target coverage and dose homogeneity and dose of organ at risk were compared between SMIM and ST planning systems.Results When the dose was normalized to cover the volume of 95% CTV,85% of the shielded areas in optimal SMIM planning were that of ＞ 103% high dose area,and 94% of target area was covered.The study on the volume of breast CTV showed that,in the large breast group,SMIM could not only significantly reduce the high dose areas,and the maximum dose as well as the dose of organ at risk,but also enhance the dose homogeneity index.However,no such effect was not significant in the small breast group.Conclusions The simplified manual intensity modulated technique can improve target dose homogeneity in the large breast cases instead of the standard tangential technique.

In order to screen antigenic genes of Clonorchis sinensis (C.sinensis).Firstly,a cDNA expression library from adult worms of C.sinensis was successfully constructed with lambda ZAP express vector.Total RNA of C.sinensis adult worms were extracted by the Trizol reagent and mRNA were further purified through oligo-dT cellulose.The first strand eDNA was synthesized by using MMLV reverse transcriptase.After the synthesis of the second strand,the cDNA were purified by CHROMA SPIN-400 kit and then ligated with lambda ZAP express vector,then packaged in vitro and amplified.The original library contained 1.5 × 106 pfu cDNA clones,the titer of amplified library reached 1.5 × 1010 pfu/mL,in which about 99% clones were recombinants and most of insert DNA fragments were 0.4-2.0 kb.Secondly,immunoscreened using the naturely infected man serum from C.sinensis.The positive clones were sequenced and analyzed.From 2.0 × 105 recombinant clones of the eDNA library,41 positive clones were obtained.Sequence analysis indicated that the cDNAs encoded proteins including glycine rich antigen 2,proline rich antigen 2 and antigen Cs44 from C.sinensis,anothers were lower similarity to predicted protein from Nematostella vectensis,transcription elongation factor GreA from Bartonella quintana str.Toulouse and NM_132090 CG3446 gene product in Drosophila melanogaster from Schistosoma japonicum.These data may form a foundation for identifying recombinant antigens that can be used in the diagnosis or vaccination against clonorchiasis.

OBJECTIVE: To investigate the association of myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) with troponin level and left ventricle (LV) function in patients with ST-segment elevated myocardial infarction (STEMI). MATERIALS AND METHODS: Thirty-five STEMI patients who successfully had undergone reperfusion treatment within 1 week of their infarction were consecutively enrolled. All patients were referred for dynamic CT-MPI. Serial high-sensitivity troponin T (hs-TnT) levels and left ventricular ejection fraction (LVEF) measured by echocardiography were recorded. Twenty-six patients with 427 segments were included for analysis. Various quantitative parameters derived from dynamic CT-MPI were analyzed to determine if there was a correlation between hs-TnT levels and LVEF on admission and again at the 6-month mark. RESULTS: The mean radiation dose for dynamic CT-MPI was 3.2 ± 1.1 mSv. Infarcted territories had significantly lower MBF (30.5 ± 7.4 mL/min/100 mL versus 73.4 ± 8.1 mL/min/100 mL, p < 0.001) and myocardial blood volume (MBV) (2.8 ± 0.9 mL/100 mL versus 4.2 ± 1.1 mL/100 mL, p = 0.044) compared with those of reference territories. MBF showed the best correlation with the level of peak hs-TnT (r = −0.682, p < 0.001), and MBV showed a moderate correlation with the level of peak hs-TnT (r = −0.437, p = 0.026); however, the other parameters did not show any significant correlation with hs-TnT levels. As for the association with LV function, only MBF was significantly correlated with LVEF at the time of admission (r = 0.469, p = 0.016) and at 6 months (r = 0.585, p = 0.001). CONCLUSION: MBF quantified by dynamic CT-MPI is significantly inversely correlated with the level of peak hs-TnT. In addition, patients with lower MBF tended to have impaired LV function at the time of their admission and at 6 months.
Blood Volume ; Echocardiography ; Heart Ventricles ; Humans ; Infarction ; Myocardial Infarction ; Myocardial Perfusion Imaging ; Reperfusion ; Stroke Volume ; Troponin T ; Troponin

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.

Adolescent ; Adult ; Child ; Deubiquitinating Enzyme CYLD ; Female ; Humans ; Male ; Neoplastic Syndromes, Hereditary ; genetics ; Pedigree ; Skin Neoplasms ; genetics ; Tumor Suppressor Proteins ; genetics ; Young Adult