Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of PRKCG gene (rs2547362,rs3745406) and osteosarcoma susceptibility in the osteosarcoma patients and the normal population.Methods Sixtyone patients with osteosarcoma who had been admitted in our hospital from January 2011 to December 2012 and 63 healthy adults were enrolled in this study.A 2-ml peripheral blood sample was taken from each participant.The RT-qPCR method was used to detect the genotype and allele frequency distribution of PRKCG gene at rs2547362 and rs3745406 in osteosarcoma patients and normal population.Osteosarcoma patients were divided into several groups according to the clinical parameters such as age,gender,histology,tumor location,Enneking classification,tumor metastasis and therapy,and then we analyzed the relations between the genetic polymorphism and clinical parameters.Results 1) The genotype of PRKCG gene at rs3745406 included CC,CT and TT.The differences of genotypes (CC,CT,TF) and alleles (C,T) frequency distribution at rs3745406 were not statistically significant between osteosarcoma patients and the normal population (P=0.490,P=0.554).2) The genotype of PRKCG gene at rs2547362 included CC,CT and TT.The differences of genotypes (CC,CT,TT) and the alleles(C,T) frequency distribution at rs2547362 were statistically significant between the osteosarcoma patients and the normal population (P=0.006,P=0.007).3) The differences of genotypes (CC,CT,TT) and alleles (C,T) frequency distribution at rs3745406 were statistically significant between patients with metastasis and patients without metastasis (P=0.000,P=0.000).The CT and TT genotypes and the T allele carrier frequency at rs3745406 were higher in patients with metastasis than in patients without metastasis.SNPs at rs2547362 were not associated with clinical parameters.Conclusion The genetic polymorphism of PRKCG gene at rs2547362 is associated with osteosarcoma susceptibility.The TT genotype and T allele at rs3745406 are associated with metastasis of osteosarcoma,which may be a risk factor for metastasis in the osteosarcoma patients.

Objective: To explore the age related increases and characteristics of static stance balance and control strategies of 3-6 years old preschool children,and to provide a reference for the research of children s physique and the practice of physical education. Methods: Using a 2×2×3 (proprioceptive×visual×age) three factor experimental design, standing balance was tested among 105 preschool children aged 3-6 years who were subjected to static for 15 s under four standing postures from January to March 2018. Quantitatively examine the static stance balance ability based on changes in the center of pressure (COP), and quantitatively examine the posture control strategy based on COP frequency domain analysis and nonlinear analysis. Results: Among children aged 3-, 4- and 5-6 years old under the condition of open eyes / hard ground AP_ MV and ML_ MV were 18.05, 16.00, 13.40; 13.55, 11.03, 10.12 mm/s respectively; Under the condition of closed eyes/hard ground, children in three age groupsAP_ MV and ML_ MV were 21.01, 19.60, 15.10; 12.20, 10.20, 10.00 mm/s respectively among three age groups of children. The results showed that the sloshing amplitude and average sloshing velocity decrease significantly with age( P <0.01). Under the conditions of open/hard ground and closed/hard ground, the high frequency band in the left-right direction and the low frequency band in the anterior posterior direction increased significantly with age ( P <0.01). Under the condition of open eyes/hard ground, three age groups of AP_ MF and AP_ HF among three age groups of children were 29.00, 28.61, 27.20； 7.45, 7.44 6.01, respectively, indicating that the middle and high frequency bands ( P <0.01) in the anterior posterior direction decreased significantly with age. ML_FD of children aged 3-, 4- and 5-6 years old under the condition of open eyes / hard ground and closed eyes / hard ground was 1.43, 1.44, 1.52; 1.49, 1.48, 1.56/mm, AP_ FD was 1.58, 1.56, 1.52; 1.56, 1.63, 1.61; AP_MSE was 6.81, 6.90, 5.61 ; 7.25 , 7.41,6.60，respectively. The results show that the fractal dimension in the left right direction increases significantly with age, while the fractal dimension and multi scale entropy in the front back direction decrease significantly( P <0.01). Conclusion The static stance balance ability of 3-6 years old preschool children shows non linear changes with age,the static posture balance ability of 5-6 years old preschool children is significantly better than that of 3-5 years old , and the balance control strategies of 5-6 years old preschool children is different from that of 3-5 years old.

Objective To explore the clinical characteristics and prognosis of the patients of acute myocardial infarction complicated with heart failure by analyzing the prognostic factors of these patients.Methods This was a single-center prospective study of 349 patients with acute heart failure and ECG documented acute ST elevated myocardial infarction.All patients were treated with primary PCI.After PCI,clinical,angiographic and ECG characteristics,and prognosis of those with preserved (≥50％) or reduced (＜ 50％) left ventricular ejection fraction (LVEF) were assessed.Heart failure patients were divided into two groups:124 with reduced EF (HFREF) and 225 with preserved EF (HFPEF).After 367 days of average follow-up,the primary outcome and number of death were recorded.Results Of them,4 (1.8％) patients in the HFPEF group vs.6 (4.8％) in the HFREF group died.The difference in rate of death between two groups was not significant (P =0.314).There were significant difference in main adverse cardiac and cerebra vascular events (MACCE) occurred during follow-up period between the two groups (P =0.022).The Killip Classification of heart failure (HR =1.092,95％ CI 1.040 ～ 1.149,P ＜0.01) was significantly related to the death rate during follow-up.Conclusions The independent factors affecting prognosis in patients with acute heart failure after coronary revascularization were closely consistent with the stratums of the Killip Classification.Patients with HFPEF had a similar prognosis as those with HFREF after primary stenting.

With the rapid advancement of science and technology, the application of 3D printing technology for personalized drug manufacturing is becoming increasingly sophisticated.Compared to traditional manufacturing technology, 3D printing can easily customize preparations with specific sizes, shapes and release behaviors for personalized drug use.This review summarizes the principles of several 3D printing technologies commonly used in drug manufacturing, lists the unique advantages and application examples of 3D printing technology for pharmaceutical preparation, analyses the current research status and development trends of the global industry of drug 3D printing, and summarizes the current problems and challenges facing drug 3D printing, aiming to provide some guidance for researchers of 3D printed drugs.

Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.

Objective To observe toxic symptoms and signs , toxic damage extents and reversibility in rats after oral administration of Tangwang Mingmu granules .Methods Four dose groups with 40 rats in each group were designed in this study, including control group fed with distilled water and three groups at different dosages of the test drug .Tangwang Mingmu granules were orally administered to SD rats at the dosage of 8.4, 4.2 and 2.1 g/kg for 3 weeks and 14.0, 8.4 and 4.2 g/kg for 23 weeks, for 26 consecutive weeks .The general state of the rats was observed every day , while body mass and food consumption were calculated once a week .Halfway through and at the end of the administration (13 and 26 weeks) and after four weeks of recovery, parameters of body mass, hematology, hematological biochemistry, organ/body mass ratio and histopathology were measured .Results Compared with the control group at the same time-point, body mass of male rats in the other three groups was slightly reduced .Food consumption in high and medium dose groups was reduced (P<0.05), MCHC, ALT, TBIL and Na +in high dose group were decreased (P<0.05), TP, ALB and D-BIL were increased (P<0.05), the mean body mass and relative organ weight of thymus in medium dose male rats were decreased (P<0.05), relative organ weight of the liver and kidney in high dose male rats was increased (P<0.05), and focal chronic inflammation to different extent was observed in the liver , kidney and prostate gland .No dose-effect relationship was found in these perturbations that were all within the normal range of animals .No significant drug-related pathological changes were found.Conclusion The NOAEL of Tangwang Mingmu granules is considered to be 14.0 g/kg body mass/day (equal to 50 times the proposed clinical adult dosage ) for the 26-week repeated dose oral toxicity study in male andfemale rats.

OBJECTIVE To investigate the role of gonadotropin-releasing hormone (GnRH) in es-tradiol(E2 ) induced advance of puberty onset in rats. METHODS Postnatal day 18 SD rats were given a daily intragastric administration of corn oil or E2(50 μg.kg-1 ) for consecutive 5 d. The day of vaginal opening (VO), pathological changes in ovary and protein expression levels of GnRH, G protein-coupled receptor 54 ( GPR54) and phospholipase C ( PLC) in hypothalamus were observed. RESULTS As compared to corn oil controll group, VO was advanced by about 12.2 d, corpus luteum was observed in the ovary section, and the protein expression levels of GnRH,GPR54 and PLC in hypothalamus were significantly increased by 47%, 55% and 56% in E2 group, respectively. CONCLUSION E2 induced onset of puberty advance may be closely related to regulation of the expression of GnRH, GPR54 and PLC in hypothalamus.

The poorly water-soluble drug curcumin was prepared into oral nanocrystalline solid preparation by nanocrystal technology to improve the solubility, dissolution rate, and bioavailability. Curcumin nanocrystals were prepared by media grinding technology, and two types of stable curcumin nanocrystal suspension formulations were developed. The stabilizers in the two formulations were polyvinylpyrrolidone (PVP K30)/sodium lauryl sulfate (SDS)(1∶1) and Tween 80, respectively. The prepared curcumin nanocrystal suspension was loaded onto microcrystalline cellulose pellets through fluidized bed coating technology, and the nanocrystalline capsules were obtained after filling. The results of nanocrystal redispersion stability and scanning electron microscope (SEM) showed that the morphology of drug-loaded pellets was uniform when PVP K30 and SDS were used as stabilizers, and the diameter of nanocrystals before and after redispersion was about 200 nm, which was determined as the optimal formulation. In vitro dissolution study showed that curcumin nanocrystals at the size of 200 nm exhibited significantly promoted dissolution. The results of X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that the curcumin crystalline partly turned amorphous during the preparation of nanocrystals.Pharmacokinetic studies in rats showed that the bioavailability of curcumin nanocrystals was 9.3 times higher than that of the bulk drug. The curcumin nanocrystalline capsules developed in this research can significantly improve the dissolution rate and bioavailability, which is of great significance in improving the poor solubility of drugs, and is expected to become a new dosage form for clinical treatment.

Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.

SUMMARY Thehumanembryonicstemcells(hESCs)serveasaself-renewable,genetically-healthy, pluripotent and single source of all body cells,tissues and organs.Therefore,it is considered as the good standard for all human stem cells by US,Europe and international authorities.In this study,the standard and healthy human mesenchymal progenitors,ligament tissues,cardiomyocytes,keratinocytes,primary neurons,fibroblasts,and salivary serous cells were differentiated from hESCs.The human cellular health-safety of NaF,retinoic acid,5-fluorouracil,dexamethasone,penicillin G,adriamycin,lead ace-tate PbAc,bisphenol A-biglycidyl methacrylate (Bis-GMA)were evaluated selectively on the standar-dized platforms of hESCs,hESCs-derived cardiomyocytes,keratinocytes,primary neurons,and fibro-blasts.The evaluations were compared with those on the currently most adopted cellular platforms.Parti-cularly,the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endo-thelial cells (HUVECs)were evaluated.The results showed that the standardized hESCs cellular plat-forms provided more sensitivity and accuracy for human cellular health-safety evaluation.