Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Cinnabaris(α-HgS) is a mineral traditional Chinese material medica, as a tranquilizer and sedative, which is widely used in combination with herbs for the treatment of children high fever and convulsion.However, a large amount of mercury in Cinnabaris poses a potential risk to the immature central nervous system of children and probably causes severe memory disorders.Inthisstudy,three groups of juvenile rats were given low, medium, and high doses of Cinnabaris by oral gavage once a day for 14 continuous weeks, respectively.The blood mercury concentrations of the rats at different growth phases were monitored by atomic fluorescence spectrometry.The brain structural and functional changes related to the memory functions were investigated through HE staining and Morris water-maze test. Correlation analysis was conducted to clarify the dose- mercury exposure-toxic effect relationship of Cinnabaris and memory disorders.It was found thatthe blood mercury levels increased in both time- and dose-dependent manner.After the 14-week continuous administration of Cinnabaris, the pathological lesions in hippocampal neurons of rats in the high dose group were observed including pyknosis and disordered cell arrangement.In the Morris water-maze test, compared with the control group, rats in the high dose group exhibited the significantly prolonged latency to find the platform and the target quadrant, and the time spent in the target quadrant was obviously shortened. Thus, the significant correlations were established between Cinnabaris dose and mercury exposure,mercury exposure and memory disorders, respectively. In conclusion, the long-term and overdose administration of Cinnabaris in juvenile rats can increase the in-vivo mercury level, destroy the normal hippocampal morphological structure, and lead to memory disorders. This study provided scientific references for the potential mercury poisoning risks pharmacovigilance of Cinnabaris-containing paediatric formulations.

Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Female ; Humans ; Killer Cells, Natural ; Pregnancy ; Pregnancy Complications

Objective: To observe the influence on IL-1β and IL-2 in rat models with rheumatoid arthritis after moxibustion on Shenshu (BL 23) and Zusanli (ST 36) points, and to discuss the mechanism of moxibustion. Methods: Fifty male Wistar rats were divided randomly into 5 groups,control group, model group, drug group, moxibustion group, and laser group, 10 for each. Four groups except the normal group were built on the model of rheumatoid arthritis. The changes of body weight and plantar circumference were measured and the level of IL-1β、 IL-2 in sera were examined by ELISA. Results: Compared with the model group, the weight and plantar circumference of rats in the moxibustion group were improved significantly after treatment (P＜0.01), and the improvement of plantar circumference also had significant differences compared with the drug group and the laser group (P＜0.05). The level of IL- 1β、 IL-2 in sera were down regulated in the moxibustion group and the laser group, which had statistical differences compared with the model group (P＜0.05), but no statistical differences were found when comparing with the drug group. Conclusion: Moxibustion obviously improves the toe tumefaction of the rats with rheumatoid arthritis, which is better than CO2 laser of 10.6μm. On the aspect of decreasing the amount of IL-1β、 IL-2, CO2 laser of 10.6 μm is similar with moxibustion.

The solvent sublation technique was applied for the separation and enrichment of L-Arg using dodecylbenzene sulfonic (DBSA) as the surfactant, di (2-ethylhexyl) phosphoric acid (P204) as the extractant and n-heptane as the organic solution. The solvent sublation was compared with the floatation complexation extraction, foam floatation and solvent extraction. The experimental results showed that enrichment ratio of 16.2 and removal rate of 97.2% to L-Arg were obtained by the solvent sublation under the conditions of room temperature, 0.09 g/L L-Arg aqueous solution 250 mL, DBSA concentration 0.15 g/L, the initial pH 7.0, volume of n-heptane 10 mL, volume of P204 4.5 mL, gas flow rate of 200 mL/min. The study of the kinetics indicated that the solvent sublation process could be divided into three stages distinctly. The processes of the first stage and the second stage followed the first order kinetics equation; the process of the third stage followed the zero order kinetics equation. The separation mechanism of solvent sublation was also discussed.

OBJECTIVE:To optimize the formulation of dextromethorphan hydrobromide sustained-release tablets. METHODS: The dextromethorphan hydrobromide sustained-release tablets were prepared with HPMC as sustained release matrix. Orthogonal test was performed to optimize the formulation with in vitro accumulative drug release rate as index and the amount of HPMC and lactose as well as ethylcellulose (EC) concentration as factors. Then verification test on the in vitro drug release characteristics of the optimized tablets were performed and the influencing factors (high temperature,high light,and high moisture) were investigated as well. RESULTS: The optimized formulation of dextromethorphan hydrobromide sustained-release tablets was as follows: 30 mg HPMC,50 mg lactose,and 8% EC. The accumulative drug release rate at 8 h was above 70%. In the influencing factor test,the tablets were stable under all conditions except at high moisture condition. CONCLUSION: The optimized formulation of dextromethorphan hydrobromide sustained-release tablets is feasible.

OBJECTIVE:To optimize the preparation technology of roxithromycin microspheres.METHODS:The microspheres of roxithromycin were prepared by the emulsion-solvent diffusion method with ethylcellulose used as capsule wall material.The preparation technology of microspheres was optimized by orthogonal experiment taking encapsulation efficiency as index with the ratio of roxithromycin to ethylcellulose(A),the concentration of ethylcellulose(B)and the ratio of water phase to oil phase(C)as factors.The appearance,particle diameter,drug-loading amount,encapsulation efficiency,in vitro release and bitter smell were studied.RESULTS:The optimal preparation conditions were as follows:A was 1∶1,B was 30 ?g?mL-1 and C was 4∶1.The microspheres obtained were round and well-distributed with mean diameter of 75.0～90.0 ?m,drug-loading amount of 45%～46%,encapsulation efficiency of over 90% and sustained release for over 13 hours.No bitter taste of the roxithromycin-ethylcellulose microspheres was felt by the majority of subjects.CONCLUSION:The roxithromycin microspheres made by optimization technology was bitter-masked and sustained release.

OBJECTIVE:To prepare Yinxingye extract pellets and study its in vitro drug release rate.METHODS:The Yinxingye extract were coated with 3 coating materials(opadryⅡ,Eudragit L30D-55 and Eudragit S 100,respectively)to be prepared into pallets by centrifugalized palletizing method;and the 3 different coated pallets were prepared into mixed pallets in an pre-designed ratio.The in vitro release of the 3 coated pallets and the mixed-coated pallets were determined by changing the pH-gradient of media(0.1 mol?L-1 hydrochloric acid,pH 5.8 PBS,pH 7.2 PBS).RESULTS:The pallets coated with 3 different coating materials released quickly in 0.1 mol?L-1 hydrochloric acid,pH 5.8 PBS and pH 7.2 PBS,and the pellets with mixed coating materials had a sustained release until a complete release within about 8 h in pH gradient-changed media.CONCLUSION:The preparation process is feasible and provides theoretic basis for industrial production.

Objective To identify the effect of decreasing the rejection using the biological semipermeable membrane combined with the privileged site xenotransplantation. Methods The rat ICCs encapsulated by biological semipermeable membrane were xenotransplanted into dog's brain. The pathological changes of implants and surrounding cerebral tissues were observed under light and electric microscopy. The ?-cells of implants were identified by immunohistochemistry. Results After 2 months of transplantation, The ?-cells were observed and the lymphocytes were dispersed in the grafts.The brain tissues near the grafts showed slight edema and glial hyperplasia. Conclusion The method using the biological semipermeable membrane in combination with the privileged site xenotransplantation have a beneficial effect on the inhibition of the rejection of heterogeneous ICCs implant.

OBJECTIVEWolff-Parkinson-White syndrome (WPW) is considered to be an autosomal dominant hereditary disease, but the gene is not identified. The objective of this study was to localize the genetic loci of Wolff-Parkinson-White syndrome.

METHODSLinkage analysis between the disease of Wolff-Parkinson-White syndrome and 3 STR (short tandem repeats) markers on 7q3 (D7S505, D7S688, and D7S483) was tested in 3 kindreds of the Wolff-Parkinson-White syndrome (101 numbers in total) by genotyping.

RESULTSWolff-Parkinson-White syndrome was linked to the loci above. The maximum two-point Lod score detected at D7S505 was 6.4 at a recombination fraction (theta) of 0.1; the Lod score of D7S688, D7S483 was 5.3 vs 2.5.

CONCLUSIONThe gene of Wolff-Parkinson-White syndrome is located at 7q3.

Adolescent ; Adult ; Child ; Chromosome Mapping ; Chromosomes, Human, Pair 7 ; Female ; Genetic Markers ; Humans ; Male ; Middle Aged ; Tandem Repeat Sequences ; Wolff-Parkinson-White Syndrome ; genetics