AIMTo prepare solid lipid nanoparticles (SLN) loaded with all trans retinoic acid using an ultrasonic technique with Compritol 888 ATO as matrix material, and investigate properties of nanoparticles in vitro and in vivo.

METHODSUltrasonic technique was adopted to prepare solid lipid nanoparticles in an aqueous system using all-trans retinoic acid (ATRA) as a model drug. Physicochemical proterties of SLN were investigated in detail. Drug release from two sorts of ATRA-SLN was investigated using a dialysis bag method. Compared with ATRA solution, the in vivo pharmacokinetics of two sorts of ATRA-SLN after intravenous injection to rats were studied.

RESULTSSolid lipid nanoparticles loaded with all-trans retinoic acid was readily and quickly prepared by ultrasonic technique. The morphological investigation by Transmission Electron Microscopy (TEM) showed that the particles had round and uniform shapes. The mean diameters of them were (158 +/- 9) nm and (89 +/- 11) nm separately. The SLN dispersion was stable at 4 degrees C for more than one year. Drug loading was 3.3%, drug entrapment efficiency was more than 95%, the in vitro release was well in accordance with Weibull distribution. Compared with ATRA control solution, SLN could stay in the blood circulation for a longer time after intravenous injection.

CONCLUSIONThe ultrasonic technique was appropriate for the preparation of solid lipid nanoparticles.

Animals ; Drug Carriers ; Drug Delivery Systems ; Drug Stability ; Fatty Acids ; Male ; Nanostructures ; chemistry ; Particle Size ; Poloxamer ; chemistry ; Polysorbates ; Rats ; Rats, Wistar ; Tretinoin ; administration & dosage ; pharmacokinetics ; Ultrasonics

China ; epidemiology ; Congenital Hypothyroidism ; diagnosis ; epidemiology ; Humans ; Infant, Newborn ; Neonatal Screening

OBJECTIVETo investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats.

METHODSTotally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot.

RESULTSCompared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05).

CONCLUSIONSShenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.

Animals ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Angiopathies ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the influence of the changes in the levels of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) on cardiac function of severe burn patients during shock stage.

METHODSSixty severe burn patients with total burn surface area larger than 30% were enrolled as experiment group (E group) , and they received fluid resuscitation and debridement during shock stage. Sixty healthy volunteers were enrolled as control group (C group). The changes in the plasma level of CGRP, NPY and cTnT in E and C groups were observed at 1, 3, 6, 12, 24, 48 post-burn hours (PBH). The correlation among the CGRP, NPY and cTnT in the C group were analyzed.

RESULTSAt 3 PBH, the plasma level of CGRP in E group (28 +/- 6) ng/L was lower than that in C group (55 +/- 7) ng/L , and it reached the lowest level at 12 PBH (15 +/- 4)ng/L . It was still lower than that in C group at 48 PBH (P < 0.05). The levels of NPY and cTnT in E group were significantly increased at 1PBH [(136 +/- 20) ng/L, (0.41 +/- 0.08) microg/L] compared with that in C group[ (86 +/- 13) ng/L, (0.16 +/- 0.06) microg/L], peaking at 12PBH [(189 +/- 31) ng/L, (1.78 +/- 0. 47) microg/L], and remaining higher than those in C group at 48PBH. There exhibited obvious negative correlation between the changes in the level of CGRP and cTnT ( r = -0.76, P < 0.01), while obvious positive correlation was found between the changes in level of NPY and cTnT ( r = 0.79, P < 0.01).

CONCLUSIONThe decrease in CGRP level and the increase in NPY level might play important roles in myocardial injury during shock stage of severe burn patients.

Adult ; Burns ; blood ; physiopathology ; Calcitonin Gene-Related Peptide ; blood ; Female ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; Neuropeptide Y ; blood ; Shock, Traumatic ; blood ; physiopathology ; Troponin T ; blood

BACKGROUNDBiliary cast syndrome (BCS) was a postoperative complication of orthotopic liver transplantation (OLT), and the reason for BSC was considered to relate with ischemic type biliary lesions. This study aimed to evaluate the relationship between BCS following OLT and the hepatic artery resistance index (HARI), and to observe pathological changes and morphology of biliary casts.

METHODSTotally, 18 patients were diagnosed with BCS by cholangiography following OLT using choledochoscope or endoscopic retrograde cholangiopancreatography. In addition, 36 patients who did not present with BCS in the corresponding period had detectable postoperative HARI on weeks 1, 2, 3 shown by color Doppler flow imaging. The compositions of biliary casts were analyzed by pathological examination and scanning electron microscopy.

RESULTSHARI values of the BCS group were significantly decreased as compared with the non-BCS group on postoperative weeks 2 and 3 (P < 0.05). Odds ratio (OR) analysis of HARI 1, HARI 2, HARI 3 following the operation was >1 (OR = 1.300; 1.223; and 1.889, respectively). The OR of HARI 3 was statistically significant (OR = 1.889; 95% confidence interval = 1.166-7.490; P = 0.024). The compositions of biliary casts were different when bile duct stones were present. Furthermore, vascular epithelial cells were found by pathological examination in biliary casts.

CONCLUSIONSHARI may possibly serve as an independent risk factor and early predictive factor of BCS. Components and formation of biliary casts and bile duct stones are different.

Aged ; Biliary Tract Diseases ; pathology ; Cholangiopancreatography, Endoscopic Retrograde ; methods ; Female ; Hepatic Artery ; surgery ; Humans ; Liver Transplantation ; adverse effects ; Male ; Middle Aged

OBJECTIVETo assess the association between polymorphisms of protein-activated inwardly rectifying K+ channel (GIRK4) gene and insulin resistance (IR) in Xinjiang Uygur population.

METHODSA cross-sectional epidemiological survey-based case-control study was carried out, for which 1295 subjects (including 324 IR patients and 971 non-IR controls) were randomly selected. Functional region of the GIRK4 gene was sequenced for 48 randomly selected IR patients. Representative variable sites were chosen, with its association with IR assessed in 1295 Uygur subjects.

RESULTSrs11221497 variant was associated with IR in Uygur subjects under 50 years old (P=0.017 in genotype model, P=0.009 in dominant model). Subjects with dominant model of CC genotype have an OR of 1.833 (95%CI: 1.157-2.905) for IR.

CONCLUSIONGIRK4 gene polymorphisms may be associated with IR in Uygur ethnics from Xinjiang. The CC genotype of rs11221497 variant is a risk factor for IR.

Adult ; Alleles ; Case-Control Studies ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Insulin Resistance ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors

OBJECTIVETo explore the association between early menarche and physical fitness among adolescent girls in China.

METHODSResearch material was selected from the data of "2010 National Physical Fitness and Health Survey". Probability unit regression method was used to calculate the age of 10th percentile at menarche and menarche age before the 10th percentile was defined as early menarche(9.0-11.6 years old). A total of 1072 girls with early menarche were selected. Each girl with early menarche was matched with one girl from the same urban or rural locations who hadn't achieved menarche with the age difference less than 0.1 years. A total of 1072 girls without menarche were selected. Indicators of physical fitness included 50 m running, standing broad jump, 50 m×8 shuttle running and sit-ups. Differences of physical fitness between early menarche and without menarche were analyzed using t test stratified by age and urban/rural area. The multilevel models of single dependent variable and multiple dependent variables were used to analyze association between early menarche and physical fitness.

RESULTSA total of 2144 students were put in this research. Among girls (11.0-11.6 years old) in urban areas, 50 m running, standing broad jump and sit-ups was (9.78 ± 0.85) s, (153.81 ± 18.59) cm, and 27.79 ± 10.25, respectively for those with early menarche, while in girls without menarche was (10.01 ± 0.90) s, (149.71 ± 18.72) cm and 26.28 ± 10.11, respectively. There were significant differences between two groups on all above variables (t values were 4.02, 3.43 and 2.31, respectively with all P values <0.01). Among girls in rural, 50 m×8 shuttle-running and sit-ups was (125.22 ± 15.57) s and 24.96 ± 8.97 for those with early menarche, while it was (120.92 ± 13.06) s and 22.96 ± 9.83 for those without menarche. There were significant differences between two groups on both variables(t values were 3.89 and 2.77 with both P values < 0.01). In addition, 50 m×8 shuttle-running in girls (10.0-10.9 years old) with early menarche was (128.52 ± 15.74) s and it was (123.89 ± 13.50) s in girls without menarche. The difference was significant (t = 2.14, P < 0.05). The multilevel analysis showed that 50 m running, standing broad jump and sit-ups in girls with early menarche was 0.12 s, 3.14 cm and 1.11 higher than girls without menarche (Waldχ(2) values were 4.00, 6.22 and 4.07, respectively with all P values < 0.05). But 50 m×8 shuttle-running in girls with early menarche was 1.95 s less than girls without menarche (Waldχ(2) = 3.96, P < 0.05).

CONCLUSIONEarly menarche may be associated with higher speed fitness, leg power and muscle power and lower physical stamina.

Child ; China ; Female ; Humans ; Menarche ; physiology ; Models, Statistical ; Physical Fitness ; physiology ; Rural Population ; Students ; Urban Population

OBJECTIVETo investigate the relationship between the G protein-gated inward rectifier K+ channel subunit 4 (GIRK4) gene polymorphism and the dyslipidemia among Uyghur residents in Xinjiang.

METHODSThe polymorphisms of rs2604204, rs4937391, rs6590357, and rs11221497 among the Uyghur residents were genotyped using Taqman polymerase chain reaction (PCR). Lipid levels were measured by conventional methods and were analyzed.

RESULTSIn the less-than-50-years population, the genotype distributions of the rs6590357 was statistically significant different in subjects with or without abnormal triglycerides (P=0.005). Aslo, the the genotype distributions of the rs11221497 also significantly differed in subjects with normal compared or abnormal TG (P=0.011). Logistic regression analysis suggested that rs6590357 still had positive association with TG abnormalities in subjects under 50 years (P=0.014). rs11221497 also had positive association with TC abnormalities. The TG levels of CT+TT genotypes were significantly higher than the CC group (P=0.006). Haplotype analysis found that the differences of H3 haplotype frequencies between the TG abnormal and normal groups were statistically significant (P=0.007).

CONCLUSIONThe polymorphisms of rs11221497 and rs6590357 of GIRK4 gene may play a role in the development of dyslipidemia in Uygur population.

China ; epidemiology ; Dyslipidemias ; epidemiology ; metabolism ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Potassium Channels, Inwardly Rectifying ; genetics ; Triglycerides

OBJECTIVETo construct a breast cancer gene-drug network model for extracting and predicting the correlations between breast cancer-related genes and drugs.

METHODSWe developed an algorithm based on the ABC principle and the association rules to obtain the correlations between the biological entities. For breast cancer, we constructed 3 different correlations (gene-gene, drug-drug and gene-drug) and used the R language to implement the associated network model. The reliability of the algorithm was verified by ROC curve.

RESULTSWe identified 185 breast cancer-associated genes and 98 associations between them, 97 drugs and 170 associations between them. The breast cancer genes-drugs network contained 127 genes and 77 drugs with 384 associations between them.

CONCLUSIONSWe identified a large number of different correlations between the breast cancer-related genes and drugs and close correlations between some biological entity pairs that have not yet been reported, which may provide a new strategy for experimental design for testing personalized breast cancer treatment.

Algorithms ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; Female ; Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; ROC Curve ; Reproducibility of Results

OBJECTIVETo explore the influencing factors on physical endurance among Chinese primary and middle school students aged 10-17.

METHODSData was used from "2010 National Physical Fitness and Health Surveillance", from which 68 458 primary and middle school students with complete information were selected. Good physical endurance was defined as endurance running time ≤ P 25 of same gender and age, poor physical endurance as ≥ P 75 of same gender and age. Difference of endurance running time in different physical endurance groups was compared; chi-square test, logistic regression and multiple level model were used to analyze influence of region, BMI, diet, exercise and exercise willingness on physical endurance.

RESULTSThere were 34 293 (50.0%) students of good physical endurance and 34 219 (50.0%) ones of poor physical endurance in 68 458 subjects. Percentage of good physical endurance was 53.8% (18 285/33 996) in rural students, higher than urban ones (46.3% (15 954/34 462)) (χ(2) = 384.16, P < 0.01). Percentage of good physical endurance was 12.2% (448/3660) in obese students, lower than normal (55.2% (28 183/51 028)), overweight (29.3% (2012/6874)) and emaciated ones (52.1% (3596/6896)) (χ(2) = 3840.08, P < 0.01). Percentage of good physical endurance was 52.5% (25 534/48 679) in students having breakfast everyday, higher than ones never having breakfast or 1-2 times per week (41.3% (3209/7768))(χ(2) = 438.31, P < 0.01). Percentage of good physical endurance was 51.7% (11 580/22 379) in students having milk everyday, slightly higher than ones never or sometimes having milk (49.2% (22 659/46 079)) (χ(2) = 39.84, P < 0.01). Percentage of good physical endurance was 55.3% (18 961/34 314) in students with adequate physical education class, higher than ones with inadequate class (44.7% (15 278/34 144)) (χ(2) = 756.41, P < 0.01). Percentage of good physical endurance was 58.6% (9484/16 195) in students with one hour exercise or more per day, higher than ones with less than one hour exercise (47.4% (24 755/52 263)) (χ(2) = 619.82, P < 0.01). Percentage of good physical endurance was 60.1% (19 287/32 118) in students who were "very willing" to take part in endurance running, higher than "generally willing" ones (45.4% (10 569/23 272)) and "not willing" ones (33.5% (4383/13 068)) (χ(2) = 2909.61, P < 0.01). Multiple level analysis revealed that risk of poor physical endurance was lower in rural students (OR = 0.80, 95%CI: 0.77-0.82) than urban ones. Risk in emaciated students (OR = 1.11, 95%CI: 1.05-1.17), overweight students (OR = 2.69, 95%CI: 2.55-2.85) and obese students (OR = 7.71, 95%CI: 6.97-8.52) was higher than normal ones. Concerning diet, risk of poor physical endurance in students never having breakfast or once to twice per week was highest (OR = 1.20, 95%CI: 1.13-1.26), followed by students having breakfast three to five times per week (OR = 1.13, 95%CI: 1.08-1.18); risk in students having one bag of milk per day was higher (OR = 1.09, 95%CI: 1.02-1.17) than ones having two bags. Concerning exercise, risk of poor physical endurance in students with inadequate physical education class (OR = 1.20, 95%CI: 1.13-1.26) and less than one hour exercise per day (OR = 1.34, 95%CI: 1.29-1.40) was higher than ones with adequate physical education class and one hour exercise or more respectively. Risk of poor physical endurance in students who were "generally willing" (OR = 1.67, 95%CI: 1.61-1.73) and "not willing" (OR = 2.72, 95%CI: 2.60-2.85) to take part in endurance running was higher than "very willing" ones.

CONCLUSIONUrban and rural residence, BMI, breakfast, milk, physical education class, exercise time and exercise willingness were related to primary and middle school students'physical endurance.

Adolescent ; Child ; Female ; Humans ; Male ; Models, Statistical ; Physical Endurance ; Physical Fitness ; Students