Src is a non-receptor protein tyrosine kinase activated by a number of extracellular signal moleculars. It is recruited to peripheral sites through myristoylation and the SH3 domain. Src initiates intracellular signal trandsduction pathways that influence cell adhesion, migration, growth, differentiation and survival though catalytic domain. Src is normally maintained in an inactive conformation because of carboxy terminal Src kinase, but can be activated transiently during cellular events such as mitosis or constitutively by abnormal events such as mutation and some cancers. In additions, c-Src protein is found to be highly activated and the Src gene is frequently over-expressed in many cancers. These findings suggest that the relationship between c-Src activation/over-expression and cancer progression appears to be significant.

Liposomes can be cleared by the reticuloendothelial system (RES) when it is in the blood circulation in the body. And they can accumulate in the organs rich in RES in the body by passive targeting. Targeting of the liposomes is an important factor for its use as a drug carrier, and particle size as well as surface charge are important for its in vivo targeting. In this paper, studies on the influences of particle size and surface charge of the liposomes on cell binding and phagocytosis mechanism were reviewed. A comprehensive review on passive targeting effect of the particle size and surface charge of liposomes on blood, liver, spleen as well as tumor tissue was made. At last, an outlook for future research directions was made.

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.

Pharmaceutical preparations can directly affect the administration methods and therapeutic effects of drugs , which is a priority for the research and development of the military specialized medicament .Foreign armies started pharma-ceutical formulation research very early , and some of their research concepts and strategies are worth learning from .In this paper , dosage forms were used as the classification factor and several formulations with distinct military characteristics were described in detail .The features of military specialized medicament were analyzed from the perspective of pharmaceutics , based on which future development in the formulation of military specialized medicament was predicted .

Objective To observe the effects of positive end-expiratory pressure(PEEP) on oxygen utiliza-tion coefficient in patients with acute respiratory distress syndrome(ARDS). Methods 28 ARDS patients with me-chanical ventilation were studied. Catheter of central vein was laid. Increment levels of PEEP(0,5, 10, 15 and 20cmH2O) were applied sequentially. Hemodynamics and oxygen metabolism parameters were measured and calcula-tion of O2 UC [O2 UC = (SaO2 -SvO2.)/SaO2] were carried out respectively. O2 UC in 30 normal subject groups were carried out. Results Arterial oxygen tension(PaO2) increased significantly(P < 0.05) at PEEP 5cmH2O. Oxygen u-tilization coefficient (O2 UC), heart rate(HR) and mean blood pressure (MBP) were not significantly different (P >0.05) at PEEP 10cmH2O. At PEEP 15cmH2 O, O2UC and HR increased significantly (P < 0.05), but M BP reduced obviously(P < 0.05). Conclusions Too high PEEP can result in oxygen utilization coefficient of ARDS patient de-acend furthur, can not really correct oxygen difieiency condition in patients' organization cell. The optimal PEEP should be found, and blood capacity should be appropriately increased.

Objective To compare the pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) in the patients undergoing spinal surgery in prone position supported by a Wilson frame.Methods Forty patients,of ASA physical status Ⅰ or Ⅱ,aged 30-64 yr,with body mass index ＜ 30 kg/m2,scheduled for elective spinal surgery in prone position supported by a Wilson frame under general anesthesia,were randomly allocated to receive mechanical ventilation using either VCV (n =20) or PCV (n =20) mode.Endotracheal intubation and mechanical ventilation were performed after induction of anesthesia.The tidal volume (VT) was set at 10 ml/kg according to the ideal body weight in group VCV.The maximal inspiratory pressure of the anesthesia machine was adjusted to maintain the VT at 10 ml/kg in group P.Both ventilation modes were required to maintain PET CO2 within the normal range.VT,respiratory rate,minute ventilation (MV),dynamic lung compliance (Cdyn),peak and mean airway pressure (Ppeak,Pmean),mean arterial pressure (MAP) and HR were recorded at 10 min after the patients were turned to supine position and at 30 min after the patients were turned to prone position after intubation.Arterial blood samples were collected for blood gas analysis,and oxygenation index(OI) and physiologic dead space fraction (VD/VT) were calculated.Results Compared with those at 10 min after turning to supine position,Ppeak was significantly increased and Cdyn,VT and MV were decreased at 30 min after turning to prone position in both groups.Compared with group VCV,Ppeak was significantly decreased,respiratory rate and Cdyn were increased,and no significant change was found in VT,MV,OI,VD/VT,Pmean,MAP and HR in PCV group.Conclusion Compared with VCV,PCV can improve the ventilatory efficacy and reduce the influence of prone position on respiratory dynamics in the patients undergoing spinal surgery in prone position supported by a Wilson frame.

Objective To study the relationship between the fbxl 20 gene、E-cadherin gene and the clinocopathologic features ,respectively , and the correlation about the fbxl 20 and the set gene .Methods The mRNA expression level of fbxl 20 and E-cadherin gene in 50 pairs of human colorectal adenocarcinoma tissues and matched normal tissues were detected by RT -PCR.Results The mRNA expression level of fbxl 20 gene in tumor tissues were significantly increased than that in normal tissues (0.479 ±0.141 vs.0.296 ±0.121,P=0.001),while the E-cadherin were decreased (0.440 ±0.026 vs.0.741 ±0.059,P=0.000).There was no found on the correlation between the mRNA expression level of fbxl 20 and the E-cadherin gene in the 50 tumor tissues(r=-0.165,P=0.251).However,the E-cadherin expressed level was negatively correlated with the fbxl 20 expressed level in the lower differentiation degree、in the high differentiation degree and the Duke′s D tumor tissues(r=-0.600,P=0.008;r=-0.784,P=0.017;r=-0.643,P=0.032).Conclusions The decreased mRNA expression level of E -cadherin in tumor tissues are largely due to the increased fbxl 20 gene expressed level ,which is related with the high mobility and invasion ability of the advanced tumor .

Objective To investigate the pathologic mechanism of radiofrequency ablation ( RFA ) combined with intravenous infusion of thermosensitive liposome encapsulated vinorelbine (TL-Vin) in treating liver tumors, and to analyze the effect of combination therapy on the long-term survival rate. Methods H22 liver adenocarcinoma tissue was subcutaneously implanted into ICR mice to establish the animal models. At the first experimental period, 40 mice were randomly and equally divided into 5 groups to receive different therapeutic scheme (using different TL-Vin concentrations). Twenty-four hours after the treatment the tumor specimens were collected, the necrotic areas were measured separately, and the optimal TL-Vin concentration was determined. At the second experimental period, 13 mice were randomly selected to receive treatment. Half an hour after the treatment the tumor tissues were collected and the TL-Vin concentration within the tumor was determined. At the third experimental period, 32 mice were randomly and equally divided into 4 groups, and 90 days after treatment the tumor growth curve was drawn. The survival rate was compared between each other of the groups. Results Compared with pure RFA group, TL-Vin + RFA significantly increased tumor coagulation extent (P<0.01). But free-VIN+RFA had similar tumor necrotic extent as that produced by RFA alone (P>0.05). Tumor coagulation area in TL-Vin + RFA group was bigger than that in free-VIN + RFA group at the concentration of 10 mg/kg [(341.8 ± 65.4)mm2 vs (225.3 ± 25.4)mm2, P < 0.01]. In TL-Vin group the coagulation margin was clear. The mean intratumoral Vinorelbine accumulation in TL-Vin + RFA group was 10 folds of that in free-Vin group [(1 156.5 ± 158.3)ng/ml vs (194.5 ± 52.3)ng/ml, P = 0.005]. TL-Vin +RFA had better survival result than that of RFA alone (37.6 ± 20.1 days vs. 23.4 ± 5.0 days, P=0.015), as well as than that of free-Vin + RFA [(37.6 ± 20.1)days vs (23.3 ± 1.2)days, P = 0.016]. Conclusion Thermosensitive liposomal chemotherapies (Vinorelbine) can be selectively delivered at the edge of RFA coagulation area and thus effectively increase RFA-induced tumor coagulation and prolong the end-point survival in experimental mice.

An on-line solid phase extraction ( SPE ) coupled with HPLC-MS/MS method was developed to determine S-ammuxetine and R-ammuxetine in rat plasma. The sample preparation consisted of the following steps:A protein precipitation extraction used methanol and acetonitrile ( 50:50 , V/V ); an on-line SPE treatment to remove most matrixes in plasma;an enrichment and separation step used a C18 analytical column. S-and R-ammuxetine were determined by tandem mass spectrometry. The SPE column was a Retain PEP Javelin (10 mm × 2. 1 mm × 5 μm), while the chromatographic separation was achieved using a ZORBAX SB-C18 (50 mm × 2. 1 mm × 3. 5 μm) analytical column with an isocratic mobile phase composed of acetonitrile-water-formic acid (40:60:0. 1, V/V/V, 0. 3 mL/min). The selected reaction monitoring mode of the positive ion was performed and the precursor to the product ion transitions of m/z 292 . 1/154 . 0 and m/z 260. 4/116. 2 were used to measure S-ammuxetine, R-ammuxetine and internal standard (propranolol). The method was linear over a concentration range from 0 . 2 to 1000 μg/L with the correlation coefficients of 0 . 9903 and 0 . 9951 . The average intra-day precision values were 1 . 2% -12 . 0% for S-ammuxetine and 0. 4%-11. 2% for R-ammuxetine, respectively. The average recoveries were 94. 2%-101. 6% for S-ammuxetine and 94. 3% -109. 4% for R-ammuxetine. Compared to the literature, the sensitivity of this method increased dramatically. The present method has been successfully applied to the preclinical rat research of ammuxetine isomers following intragastric administration.

Objective:Use the droplet digital PCR (ddRCR) technology to establish, optimize and evaluate the method of EGFR-T790M mutation detection.Methods:The relevant probes and primers were designed for EGFR-T790M mutations. The ddPCR reaction system was established, the optimal annealing temperature was set and the basic performance of the method was tested. On this basis, from January 2019 to October 2019, 72 cell-free DNA (cfDNA) samples from NSCLC patients were collected from Shandong Cancer Hospital Affiliated to Shandong First Medical University, and clinically verified. The consistency of the gene mutation detections with Bole ddPCR products was analyzed using Kappa test.Results:The ddPCR reaction system was established and optimized. Linear evaluation showed the R2 value was greater than 0.99. Using ddPCR, the blank detection limit was determined to be the numbers of mutant droplets≥2, with excellent specificity. For the sensitivity analysis, the lower limit of mutation detection was determined to be at least 0.05%. In the repeatability and inter-assay precision tests, the results had a coefficient of variation( CV)<20%. The relative deviation of the results was within the range of±10% for the accuracy analysis. Using the established T790M mutation detection method, 72 samples from the NSCLC patients were tested for genetic mutation in cfDNA, and the overall agreement with the Bole ddPCR products was 91.67% (66/72, Kappa=0.749; P<0.001). Conclusion:Using ddPCR, the method of EGFR-T790M mutation detection for NSCLC was successfully established.