In this study, we investigated the pharmacokinetics parameters of SPIO-shRNA dual functional molecular probe and observed the main organ distribution by MRI in vivo. Eighteen New Zealand white rabbits were randomly divided into three groups and injected intravenously with different doses of SPIO-shRNA molecular probe, respectively. The blood samples were collected to analyze the pharmacokinetic parameters by measuring the iron content at 30 minutes before and after the injection. Twenty-four Kun Ming (KM) mice were randomly divided into 4 groups: the control group was injected intravenously with physiological saline 200 µL per mouse via the tail vein, the other 3 groups were injected intravenously with different doses of SPIO-shRNA molecular probe. MRI observation was performed in 24 hours, and the liver, spleen, kidney, brain and muscle were collected for iron quantification with Prussian blue staining to determine distribution of the SPIO-shRNA molecular probe in the main organ in vivo. Our results suggest that the molecular probe blood half-life is more than 3 hours. The data of MRI suggest the probe was distributed in liver and spleen, and the MRI signal was reduced with the increase in probe's doses (P < 0.05). The results of Prussian blue staining confirmed the results of MRI. Most of the probe could escape the phagocytosis of mononuclear phagocyte system. Our data provide the pharmacokinetic and distribution of SPIO-shRNA molecular probe in organs. Meanwhile, it suggests the choice of the time and dose of probe for MR imaging of tumor in vivo.
Animals ; Half-Life ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Mice ; Molecular Probes ; pharmacokinetics ; RNA, Small Interfering ; chemistry ; Rabbits

OBJECTIVETo compare the clinical effects of Cookgas intubating laryngeal airway (CILA) in facilitating fiberoptic bronchoscope (FOB) and Shikani optical stylet (SOS)-guided intubations in anticipating difficult tracheal intubation.

METHODSTotally 60 anticipated difficult tracheal intubation patients undergoing selective plastic surgery under general anesthesia were allocated to FOB group (n = 30) and SOS group (n = 30). After anesthesia induction and CILA insertion, the patients were treated with FOB or SOS-guided intubation via CILA. The time of intubation and CILA removal and the time and the success rate of CILA insertion were recorded. Noninvasive blood pressure and heart rate were recorded before and after anesthesia induction at CILA insertion, at intubation, at CILA removal, and every minute thereafter for 5 minutes.

RESULTSCILA was inserted successfully in all patients. The first intubation attempt succeeded in all but two who succeeded in the second and the third attempt respectively in FOB group. In SOS group, 18 patients were successfully intubated in the first attempt, and 7 patients were successfully intubated in the second attempt; SOS failed in 5 patients with severe cervical scars, and then FOB was successfully used to intubate. The time of the intubation [(60.2 +/- 29.6) vs. (92.4 +/- 47.9)s] and CILA removal [(104.6 +/- 39.9) vs. (130.0 +/- 51.9) s] in SOS group were significantly longer than in FOB group (P < 0.05). Hemodynamic changes during the intubation with CILA in these two groups were minimal.

CONCLUSIONSFOB and SOS-guided tracheal intubation via CILA is safe and effective in anticipating the outcome of difficult airway management. Compare to SOS-guided intubation, the time of FOB-guided intubation is shorter and the success rate is higher.

Anesthesia, General ; Bronchoscopes ; Fiber Optic Technology ; Humans ; Intubation, Intratracheal ; adverse effects ; methods ; Observation ; Surgery, Plastic ; Task Performance and Analysis ; Treatment Outcome

OBJECTIVETo observe the clinical effectiveness of inductions and tracheal intubating conditions with 3% sevoflurane and different doses of remifentanil without muscle relaxant in children.

METHODSTotally 120 peadiatric patients (aged 4-10 years, American Society of Anesthesiologists grade I for inhalational induction) were randomly allocated into group I (remifentanil 1 microg/kg), group II (remifentanil 2 microg/kg), group III (remifentanil 3 microg/kg), and control group (vecuronium bromide 0.1 mg/kg). After inhalational induction with 3% sevoflurane and 60% nitrous oxide in 40% oxygen for 2 minutes, remifentanil 1 microg/kg, 2 microg/ kg, and 3 microg/kg were intravenously injected over 1 minute into patients in group I , group II, and group III, respectively. After remifentanil administration and manual ventilation for 1 minute, the trachea was intubated. In the control group, 2 minutes after intravenous administration of vecuronium bromide 0.1 mg/kg, tracheal intubation was attempted. Agitation, intubating satisfactoriness, and the circulation changes after tracheal intubation and anesthesia induction were observed.

RESULTSIn these four groups, agitation occurred in 37.5% of patients during sevoflurane induction. Satisfactory intubation rate was 70.0% in group I, 86.7% in group II, 90.0% in group III, and 93.3% in the control group. Compared with the control group, the impact of tracheal intubation on the circulatory system was smaller in group I , II , and III.

CONCLUSIONSInduction with 3% sevoflurane combined with remifentanil can be smoothly performed, followed by the successful tracheal intubation. The intubating conditions are more satisfactory with 3% sevoflurane combined with remifentanil 2 microg/kg or 3 microg/kg.

Anesthesia, Inhalation ; Anesthetics, Inhalation ; administration & dosage ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Intubation, Intratracheal ; adverse effects ; Male ; Methyl Ethers ; administration & dosage ; Piperidines ; administration & dosage

AIM:To screen the differentially expressed long non-coding RNA(lncRNA)in colon cancer,and to explore its expression in colon cancer tissues and adjacent tissues.METHODS:The "Colon adenocarcinoma:Person neoplasm cancer status" which consisted of 36 cases of colon cancer tissues and 29 cases of normal colonic tissues was downloaded from the lncRNAtor database.The candidate genes were selected from these differentially expressed lncRNAs based on artificial criterion(P<0.01;fold change ≥2 or<0.5)and then validated by real-time PCR in 60 pairs of colon cancer tissues and adjacent tissues.RESULTS:A total of 50 lncRNAs were differentially expressed in colon cancer tis-sues,including 28 up-regulated and 22 down-regulated(P<0.01).The verifying results displayed that HNF1A-AS1 and ZDHHC8P1 were up-regulated(P<0.01),and SUZ12P expression was down-regulated(P<0.05),but the expression of AC069513.3 was not statistically significant between colon cancer tissues and adjacent tissues.The abilities of HNF1A-AS1,ZDHHC8P1,SUZ12P and AC069513.3 to discriminate the colon cancer from normal adjacent tissue by the ROC curve with an AUC of 0.729(sensitivity 78％,specificity 67％),0.617(sensitivity 68％,specificity 55％),0.689(sensitivity 66％,specificity 55％)and 0.518(sensitivity 52％,specificity 48％)were observed.CONCLUSION:Long non-coding RNA HNF1A-AS1 and ZDHHC8P1 are up-regulated and SUZ12P is down-regulated in colon cancer tis-sues,suggesting that they may be involved in the pathogenesis of colon cancer.

OBJECTIVETo explore the transfection rate of SPIO-shRNA dual functional molecular probe into ovarian carcinoma SKOV3 cells in external magnetic field.

METHODSDual functional molecular probe at an iron concentration of 45 mg/L was transfected into SKOV3 cells. The cells with coexisting probe and magnetic fields were set as the intervention group,the probe-transfected cells as negative control group, and normally cultured SKOV3 without any transfection as blank control group. The transfection rate was detected by flow cytometry. Cell viability was observed by CCK-8 assay. Epidermal growth factor receptor (EGFR) expression level in SKOV3 cells was determined by real-time quantitative PCR and Western blot analysis. The signal intensity was measured by magnetic resonance imaging (MRI).

RESULTSThe transfection rate of the intervention group was (79.20 ± 3.31)%, which was significantly higher than that of negative control group (P=0.001). Compared with the negative control group,the cell viability of the intervention group significantly decreased (P=0.011), protein and mRNA expression levels of EGFR in the intervention group were significantly decreased (both P<0.05). The signal intensity on T2(*)WI in the intervention group also significantly decreased (P=0.0004).

CONCLUSIONThe external magnetic field can improve the transfection efficiency SPIO-shRNA dual functional molecular probe into ovarian carcinoma SKOV3 cells.

Blotting, Western ; Cell Line, Tumor ; Cell Survival ; ErbB Receptors ; Female ; Flow Cytometry ; Humans ; In Vitro Techniques ; Iron ; Magnetic Fields ; Molecular Probes ; Ovarian Neoplasms ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Transfection

A549 Cells ; Cell Line, Tumor ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Focal Adhesion Protein-Tyrosine Kinases ; Transforming Growth Factor beta ; Transforming Growth Factor beta1

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 μmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 μmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.
Adult ; Aged ; Alleles ; Asian People/genetics* ; Base Sequence ; Case-Control Studies ; China ; Diabetes Mellitus, Type 2/genetics* ; Dyslipidemias/genetics* ; Gene Frequency ; Genotype ; Homocysteine/blood* ; Humans ; Linkage Disequilibrium ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Middle Aged ; Polymorphism, Single Nucleotide

The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.
Adult ; Aged ; Animals ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Proliferation ; Disease Models, Animal ; Disease Progression ; Female ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Middle Aged ; Receptor, IGF Type 1 ; antagonists & inhibitors ; physiology ; Tyrphostins ; pharmacology