AIM: To establish a sensitive HPLC method for determining the concentrations of paeonol in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A single oral dose of 160 mg paeonol capsules was given to 24 Chinese healthy volunteers. Paeonol was separated on a XB-C18 column with tetrahydrofuran-methanol-water-phosphonic acid (6∶60∶34∶0.1, V∶V) as mobile phase. The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated using DAS 2.0. RESULTS: The linear range of the paeonol was 10-500 ng/mL and the determination limit was 10 ng/mL. The main pharmacokinetic parameters, as Cmax, tmax, t1/2,AUC0-3, AUC0-∞ after a single dose of paeonol capsules were (116±46)ng/mL,(1.02±0.13) h,(1.03±0.35) h, (174±45) ng/mL, (217±56) ng/mL,respectively. CONCLUSION: The HPLC method for determining paeonol concentration in plasma is rapid, sensitive and suitable for pharmacokinetic studies.

To make a preliminary study on the mechanism of Coptidis Rhizoma(CR) and Rehmanniae Radix(RR) before and after the combined administration in treating type II diabetes mellitus. The type I diabetes animal model in rats was established by fat emulsion and intraperitoneal injection with streptozotocin, in order to compare the hpyerglycemic and hypolipidemic effects of CR, RR and their combined administration of different ratio. The urinary metabolic profiling in rats of Coptidis Rhizoma and Rehmanniae Radix before and after the combined administration was analyzed by using the gas chromatography-mass spectrometry. The differences among groups in metabolome were analyzed by the principal component analysis (PCA). The biochemical index results indicated that both CR and RR before and after the combined administration could lower high blood glucose, hypertriglyceride and high cholesterol. According to the analytical results of PCA of the rats' urine samples, the CR group was the most close to the normal group, with no significant difference in CR and RR group of different combination ratios. Twelve differentiated metabolites were identified to be related to type II diabetes. Compared with the normal group, the CR-treated group showed significant increase in seven differentiated metabolites. Among CR and RR drugs with different combination ratios, CR played a major role and thus acted as the monarch drug. Whereas RR served as the ministerial drug and assisted CR to show the efficacy. This study laid a foundation for the explanation of the combination mechanism of traditional Chinese medicines.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Rehmannia ; chemistry

Objective To detect serum biomarkers for pancreatic cancer associated diabetes and establish a model for diagnosis.Methods SELDI-TOF-MS was used to detect the differentially expressed serum proteins from 17 pancreatic cancer associated diabetes patients,17 new-onset type Ⅱ diabetes patients and 17 healthy controls,then a model of biomarkers was constructed and validated by Biomarker Patterns Software 5.0.Results Twelve discriminating m/z peaks were identified in the protein fingerprints in 10 pancreatic cancer associated diabetes patients,10 new-onset type Ⅱ diabetes patients and 10 healthy controls.Among them,the three biomarkers of mass/charge ratio 6116,6695 and 8936 were used to construct the model,which could diagnose 90％ pancreatic cancer associated diabetes form control groups.Blind test of other7 samples of three groups showed that 100％ pancreatic cancer associated diabetes,71％ new-onset diabetes and 86％ healthy controls were correctly classified.After searching protein database,there were metallothionein,pancreatic progenitor cell differentiation and proliferation factor-like protein,and fibroblastic growth factor 1,which were close to the weights of the above mentioned 3 differentially expressed proteins.Conclusions SELDI can identify 3 biomarkers for pancreatic cancer associated diabetes and a reliable model for diagnosis of pancreatic cancer associated diabetes is established.

This study investigated the relationship among the severity of hearing impairment,vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled.All of the patients underwent audiometry,sensory organization test (SOT),caloric test,cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test.Significant relationship was found between vertigo and hearing loss grade (P=0.009),and between SOT VEST grade and hearing loss grade (P=0.001).The abnormal rate of oVEMP test was the highest,followed by the abnormal rates of caloric and cVEMP tests,not only in patients with vertigo but also in those without vertigo.The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo).Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010).We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo.The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo.Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs.SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients.Apart from audiometry,the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL.Better assessment of the condition will help us in clinical diagnosis,treatment and prognosis evaluation of ISSNHL.

Metabonomics approach is a science that systematically studies the regularity of changes of metabolites and reveals the nature of metabolic activities of the lives in the dynamic process of metabolism. In this study, pregnant C57BL/6J mice were randomly divided into two groups with 15 mice in each. The ones in the experimental group were intraperitoneally injected with Dexamethasone and the others in the control group with isotonic Na chloride from 10th to 12th day of gestational period. On 17.5th day, all the mice were executed. The livers were extracted and prepared into aqueous soluble liver tissue extracts. The technology of nuclear magnetic resonance (NMR) was used to detect the endogenous small molecule metabolites. Finally, through the method of principal component analysis (PCA), changes of metabolites ingredients could be determined. The experimental results showed that there was significant difference in PCA scores plot between the two groups. Furthermore, the difference was in line with that of incidence of cleft palate in the embryos between the two groups. Therefore, metabonomics results can be used to reflect the changes of metabolites group interfered by Dexamethasone in the course of pregnancy of C57BL/6J mice and this method opens up a new way for further study of pathogenic mechanism of cleft lip with or without palate.
Abnormalities, Drug-Induced ; etiology ; metabolism ; Animals ; Cleft Palate ; chemically induced ; Dexamethasone ; toxicity ; Embryo, Mammalian ; Female ; Magnetic Resonance Spectroscopy ; methods ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Pregnancy

OBJECTIVETo explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.

METHODSMale intrauterine growth restriction (IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied. The body weights of offspring rats were weighted from birth to 12 weeks of age. Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay (ELISA) respectively at 1 week, 8 weeks, and 12 weeks. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats (Week 1) and adult rats (Week 12).

RESULTSBirth weights of IUGR rats were significantly lower than those of controls until 4 weeks later, when IUGR rats caught up to controls. Between 8 and 12 weeks, the growth of IUGR rats surpassed that of controls. No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups. However, by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index. At the age of 12 weeks, IUGR rats had mild fasting hyperglycemia. In addition, hepatic PGC-1 alpha mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls (P<0.05).

CONCLUSIONSAs a result of intrauterine malnutrition, the expression of gluconeogenic genes is exaggerated in offspring. This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.

Animals ; Female ; Fetal Growth Retardation ; metabolism ; Gluconeogenesis ; Glucose ; metabolism ; Glucose-6-Phosphatase ; genetics ; Liver ; metabolism ; Male ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; RNA, Messenger ; analysis ; RNA-Binding Proteins ; genetics ; Rats ; Rats, Wistar ; Transcription Factors ; genetics

OBJECTIVETo observe the effect of Xueyou Mixture (, XYM) on blood coagulation factors and its safety in treating hemophilia.

METHODSTo the randomly selected 65 inpatients of hemophilia, XYM was administered accompanied with intravenous dripping of liver cell growth factor 60-100 mg once a day to protect the liver, with no blood products like concentrated VIII and FIX factors or blood plasma given. The treatment lasted for 3 weeks. The short-term efficacy and adverse reactions were observed. The long-term efficacy in patients was observed in a follow-up study of 6-12 months after they were discharged from the hospital but continuously took XYM orally.

RESULTSThe short-term markedly effective rate in the patients was 95.38% (62/65). After they were treated for 3 weeks, the level of FVIII factor activity increased in 56 patients of type A from (3.32+/-2.21) % to (4.18+/-2.23) %, and in 9 of type B from (4.92+/-1.81) % to (5.64+/-1.96) %. Compared with that before treatment, the difference was significant in both of them (P<0.01). No obvious adverse reaction was found in the treatment period. The follow-up study showed that in 22 patients of type A, the FVIII factor activity ratio increased from (3.25+/-2.11) % to (6.31+/-2.16) %, (8.36+/-1.05) %, and (16.38+/-2.71) % in the 2nd, 3rd and 6th month after discharge respectively, all showing significant difference to that before treatment (P<0.01); and in 4 patients of type B, it increased from (4.15+/-2.26) % to 7.8% and 11.6% (mean value) in the 2nd and 6th month respectively.

CONCLUSIONXYM could raise the activity of factors VIII and IX in patients with hemophilia, and the degree of the rise is related with the duration of the therapy, with no obvious adverse reaction, which strikes out a new path and new train of thinking for the treatment of the disease by nonblood preparation.

Adolescent ; Adult ; Blood Coagulation Factors ; analysis ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Hemoglobins ; analysis ; Hemophilia A ; blood ; drug therapy ; Humans ; Infant ; Male ; Medicine, Chinese Traditional ; Middle Aged

OBJECTIVETo understand the receiving sensibility of the points on the hand's six channels for music sound wave in the healthy persons, so as to provide experimental basis for exploring the mechanism of music treatment.

METHODSBy the radiating and receiving sound wave system, the total receiving music sound (RMS) power of the music sound wave were measured at the points of the hand's six channels and non-acupuncture in 34 healthy undergraduates.

RESULTSThere was the specific receiving sensibility at Taiyuan (LU 9). The total RMS power of the music sound wave at Daling (PC 7) and Shaohai (HT 3) in the female was stronger than that in the male.

CONCLUSIONThere is the difference in the receiving sensibility of the music sound wave at the different acupoints of different channels.

Acupuncture Points ; Female ; Hand ; Humans ; Male ; Meridians ; Music Therapy ; Vibration

The electrospray ionization-ion mobility spectrometric (ESI-IMS) technique has the potential as an analytical separation tool in analyzing polypeptides and amino acids for fast screening unknown samples in anti-chemical and biological terror attacks. A method for detecting several polypeptides and amino acids was developed based on ESI-IMS using air as drift gas at room temperature. The ion mobility of four amino acids and two polypeptides dissolved in methanol was determined on the system at elution rate of 2 mL/ min. The spectra of these compounds had characteristics of finger-printing maps. The limit of detection of this instrument for Substance P could reach 855 ng / mL in 1 min. The results showed that a small, self-contained ESI-IMS instrument with reservoirs of air could be used to quickly detect and accurately identify polypeptides and amino acids.

Objective:To identify the clinical phenotypes, diagnosis, and treatment of five children with DiGeorge syndrome finally diagnosed by gene, with review of the literature.Methods:The clinical data of five children with DiGeorge syndrome admitted to our hospital were collected and sorted out. Copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS) technology was used to diagnose the genetic etiology of the children. The relationship between phenotypes and genotype among these five children were emphatically compared.Results:The five children collected in this study were all younger than 6 months. The course of the disease was more than 2 months to 1 year. Most of the first symptoms were convulsions and/or repeated infection. All of them had different degrees of growth retardation, with or without special facial features, epilepsy, congenital heart disease, etc. The similar blood ionized calcium levels revealed hypocalcemia, but the frequency and severity of convulsions were different. The copy number variation of chromosome 22q11.21 was detected in all these five children, and the deletion fragment was between 2.56-2.6 Mb, which was mostly coincident with the classical deletion region of DiGeorge syndrome (chr22: 19009792-21452445) recorded in Decipher database. One case was suggested to be a novel mutation, and the rest were of unknown origin.Conclusions:DiGeorge syndrome has great clinical heterogeneity. CNV-seq based on NGS technology is not only conducive to accurate genetic etiological diagnosis, but also helpful for understanding the corresponding relationship between clinical phenotype and genotype of hereditary syndrome, improving clinicians′ understanding and avoiding misdiagnosis.