Child ; China ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; therapy

The liquid-chromatography-mass technology was used in the metabolomic analysis of mouse's blood 1 hour after exhaustive exercise,in order to explore the potential mechanism of Rhodiola in fatigue elimination of exhaustive exercise mouse.The exhaustive mouse model was made by loaded-swimming.A total of 24 mice were randomly divided into theRhodiola + exercise group,exercise group andno-exercise group.The dose of Rhodiola was 0.4375 g·kg-1·d-1.The loaded-swimming was conducted after two successive weeks of medication.Blood was collected 1 h after swimming for the sample preparation.The enzyme assay and anthrone colorimetry were used to test blood lactate acid and glucose,respectively.UFLC-Q-TOF was used to detect metabolic profiles of each group.The principal component analysis (PCA),orthogonal partial least squares discriminant analysis (OPLS-DA) and heat map analysis were used to compare differences among groups with score chart and to obtain the characteristics biomarkers by load chart.The results showed that the blood lactate acid level of theRhodiola+ exercise group was significantly lower than that of theexercise group.And the glucose level of theRhodiola+ exercise group was significantly higher than that of theexercise group.The metabolomic analysis showed that there were no obvious changes on 1,25-(OH)2D3,diacylglycerol (DG) and inositol triphosphate (IP3).All three materials in theRhodiola + exercise group were significantly lower than those of theexercise group.They were much closer to theno-exercise group.And all three materials were related to the increasing of muscle tension.It was concluded that Rhodiola had the function of promoting fatigue eliminating.This effect may be related to cell membrane protection,regulation of 1,25-(OH)2-D3→IP3,DG pathway,and relieving of muscle tension after exercises.

The purpose of this study was to prepare the nobiletin-loaded nanoemulsions (NOB-NE) and study its in vivo distribution in mice. The characteristics and stability of the unloaded and drug-loaded nanoemulsions were investigated. The size, apparent viscosity and pH value of NOB-NE were respectively (15.5 +/- 2.9) nm, (3.10 +/- 0.33) mPa x s and 6.56 +/- 0.05, which were all higher than those of unloaded nanoemulsions. The zeta potential of unloaded and drug-loaded nanoemulsions carried negative charge. The NOB-NE after diluted by 5% glucose solution was stable in 8 h, and there was no significant difference in the size, content and diluted stability of its preconcentrate in long-term storage. The concentration of nobiletin in plasma and tissues was determined by HPLC after intravenous administration of NOB-NE. Based on AUC(0-t), MRT and C(max), the nanoemulsions delivered more nobiletin into the brain and kidney compared to those of nobiletin solution. The brain and kidney targeting efficiency was improved. In addition, the results fitting using SAAM II software show that the higher drug concentration of the NOB-NE in the brain might be owed to the quicker transport rate from the blood to the brain, and that in the kidney relate to the probable accumulation effect. These results indicate that the in vivo distribution of NOB-NE with consistent quality in mice could be changed and its brain and kidney targeting absorption capability was enhanced comparing with nobiletin solution.
Animals ; Drug Stability ; Emulsions ; Female ; Flavones ; administration & dosage ; pharmacokinetics ; Male ; Mice ; Nanoparticles ; administration & dosage ; Tissue Distribution

OBJECTIVETo investigate the efficiency of Spanishneedles Herb eye drops in treating perimenopausal xerophthalmia in rabbits.

METHODTotally 36 rabbits (36 right eyes) were ovariectomized, and 2 months later divided into three groups: the experimental group (group A, n = 12) given Spanishneedles Herb eye drops, the control group (group B, n = 12) given PBS and the model group (group C, n = 12) given no drug. The Schirmer I test (SIT), fluorescent (FL), total tear protein, diastase activity, lactoferrin and lysozyme contents and confocal scanning microscopy were performed at before the treatment and at 1 w, 2 w, 1 mo, 2 mo after the treatment.

RESULTBefore the treatment, There was no significant difference in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity between two groups. Two months later after the treatment, both the group B and the group A showed differences degrees of changes in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity compared with that before the treatment, with statistical differences (P < 0.05); At each time point, both groups revealed statistical differences in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity (1 < 0.05). Two months later alter the treatment, densities of basal epithelial cells and inflammatory cells in the group A were (4 122 ±416) cells/mm2 and (339 ± 131) cells/mm2, while that in the group B were (3 343 ± 424) cells/mm2 and (49 ± 17) cells/mm2, with statistical differences between them (P < 0.05).

CONCLUSIONSpanishneedles Herb eye drops could effectively treat perimenopausal xerophthalmia in rabbit caused by sex hormones decline.

Animals ; Asteraceae ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Ophthalmic Solutions ; administration & dosage ; Perimenopause ; drug effects ; metabolism ; Rabbits ; Tears ; secretion ; Xerophthalmia ; drug therapy ; metabolism

A new nonviral gene vector--urocanic acid-coupled chitosan (UAC) was prepared by the reaction of the activated urocanic acid (UA) with the amine group on the chitosan (CTS). The structure of UAC was confirmed with FT-IR, 1H NMR and element analysis. The influencing factors of substitution values were studied by orthogonal test, and the substitution values of UAC increased with the prolongation of activating time of UA and the increasing ratio of UA to CTS. The condensation ability and the resistance to DNase I of UAC/pDNA were evaluated by agarose gel electrophoresis, and UAC showed good condensation ability with pDNA, well protecting pDNA from the degradation by DNase I. The particle size and zeta potential were evaluated by zetasizer, and the results showed that the UAC/pDNA complex was well stable and could easily enter into cells. The transfection studies were performed with HepG2 cells in vitro. It showed that the in vitro transfection of UAC/pDNA was efficient in HepG2 cells and could express more green fluorescent proteins than that of CTS. So the UAC is easy to prepare and a promising non-viral gene vector.
Chitosan ; administration & dosage ; chemical synthesis ; metabolism ; DNA ; genetics ; metabolism ; Deoxyribonuclease I ; metabolism ; Drug Delivery Systems ; Genetic Therapy ; methods ; Genetic Vectors ; Hep G2 Cells ; Humans ; Particle Size ; Plasmids ; Transfection ; Urocanic Acid ; administration & dosage ; chemical synthesis ; metabolism

To prepare self-assemble nobiletin proliposomes and study its pharmacokinetic behavior in rats after ig administration, and nobiletin suspension was used as control, self-assemble nobiletin proliposomes were prepared by a new proliposome preparation method, their physicochemical properties including encapsulation efficiency, particle size and stability of formed liposome were determined. Plasma concentration of nobiletin was determined by HPLC taking nimodipine as internal standard. The pharmacokinetic parameters were calculated by Kinetica 4.4 software. The encapsulation efficiency of nobiletin liposomes was more than 80%, with an average particle size of 212.1 nm and very good stability. Compared to nobiletin suspension, nobiletin liposomes possessed higher absorptive rate and longer MRT, and the relative bioavailability was 264.3% in rats. It could be concluded that self-assemble nobiletin proliposome was a simple and feasible preparation, and showed greater absorption compared with nobiletin suspension.
Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Drug Carriers ; Drug Stability ; Flavones ; administration & dosage ; blood ; pharmacokinetics ; Lecithins ; chemistry ; Liposomes ; chemistry ; Male ; Particle Size ; Rats ; Rats, Sprague-Dawley

Objective To explore the effect of upgrade of dialysate quality on the microinflammation in maintenance haemodialysis (MHD) patients. Methods Fifty-three MHD patients in Kidney Center of the First Affiliated Hospital,Medical College,Zhejiang University in January 2003 were enrolled in the prospectively study.The main end-points were survival at 8 years or weaning from haemodialysis during 8-year period including death, receiving renal transplantation or transferring to peritoneal dialysis.The endotoxin level of dialysate and patients' serum levels of interleukin-6 (IL-6),tumor necrosis factor α (TNF-α),C reaction protein (CRP),and albumin were recorded during the observation period. Results After the upgrade of water management system,endotoxin level of dialysate obviously decreased [(0.046±0.012) EU/ml vs (0.454±0.002) EU/ml,P＜0.01],and serum IL-6 [(3.947±3.624) ng/L vs (13.779±7.106) ng/L,P=0.036],TNF-α [(7.935±3.864) ng/L vs (12.804±8.017) ng/L,P=0.012] as well as CRP [(0.194±0.149) mg/L vs (0.561 ±0.309) mg/L,P＜0.01] decreased significantly,while serum albumin increased [(41.900±6.803) g/L vs (38.140±7.083) g/L,P=0.042].Hemoglobin level did not change significantly after the system upgrade,however,the dose of erythropoietin decreased [(93.0±12.7) U·kg-1·week-1 vs (131.0±10.1) U·kg-1·week-1,P=0.015]. Conclusions The upgrade of central dialysis fluid delivery and water management system by application of double reverse osmosis,high frequency heat disinfection and endotoxin filter can improve the quality of dialysate.Improvement of dialysate quality can ameliorate the microinflammation state of MHD patients.

Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis,and is relevant to the inflammatory microenvironment.Lipopolysaccharide (LPS),a cell wall constituent of gram-negative bacteria,has been reported to induce EMT of cancer cells through TLR4 signal.We previously reported that LPS promoted metastasis of mesenchymallike breast cancer cells with high expression of cyclin D 1 b.However,the role of cyclin D1b in LPS-induced EMT has not been fully elucidated.In the present study,we described that cyclin D1b augmented EMT induced by LPS in MCF-7 breast cancer cells.Cyclin D1b markedly amplified integrin αvβ3 expression,which was further up-regulated under LPS stimulation.Our results showed ectopic expression of cyclin D1b promoted invasiveness of epithelial-like MCF-7 cells under LPS stimulation.Additionally,LPS-induced metastasis and EMT in MCF-7-D1b cells might depend on αvβ3 expression.Further exploration indicated that cyclin D1b cooperated with HoxD3,a transcription factor promoting αvβ3 expression,to promote LPS-induced EMT.Knockout of HoxD3 repressed LPS-induced EMT and αvβ3 over-expression in MCF-7 cells with high expression of cyclin D1b.Specifically,all these effects were in a cyclin D1a independent manner.Taken all together,LPS up-regulated integrin αvβ3 expression in MCF-7 cells with high expression of cyclin D 1b and induced EMT in breast cancer cells,which highlights that cyclin D1b may act as an endogenous pathway participating in exogenous signal inducing EMT in breast cancer cells.

Objective To summarize our experience in prevention and treatment of stricture after esopageal burns in the past thirty years.Methods There were 168 cases in this series.Of them,158 cases underwent surgical management in this study.Modified intraluminal stenting was used in 34 cases, colon interposition without resection of strictured esophagus in 77 cases,gastric transposion with resection of the stricture in 27,repair of cervical stricture with platysma myocutaneous flap in 22,and miscellane- ous operation in 12.Eleven cases experienced operation twice or more at our department.Results Twenty-nine cases recovered after treatment with intraluminal stenting,and 5 re-experienced stricture after stent removal.One of the 5 cases with failed stent responded to bougienage,and the remaining 4 cases re- quired esophageal reconstruction later.Of the 77 colon interpositions,5 cases died postoperatively,and complications of cervical anastomotic fistula occurred in 14 cases,anastomotic stenosis in 4,and abdomi- nal incision dehiscence in 2 cases.In the 27 cases with gastric transpositions,postoperative complications of anastomotic stricture occurred in 2 cases and empyema in 1 patient.There was a cervical leak in 3 ca- ses of the 22 cases treated with the repair of cervical esopageal or anastomotic stricture with a platysma myocutaneous flap.In the 12 cases treated with miscellaneous operation,one died of intestinal obstruc- tion.All the survivors had regular diet after discharge.Conclusions Intraluminal stenting can prevent the formation of caustic esophageal stricture.The location of the cicatricial esophagus dictates whether to perform concomitant esophagectomy during esophageal reconstruction.Platysma myocutaneous flap repair is an excellent method for the treatment of severe cervical esophageal or anastomotic stricture.

AIMTo study the effect of hyaluronic acid chitosan-based microemulsion (HAC-ME) on the permeability of blood brain barrier( BBB) by using Evans blue (EB) as the indicator.

METHODSA formamide extraction-ultraviolet spectrophotometry method was employed to determine the concentrations of EB in each of the tissues. The in vivo distribution of HAC-ME groups containing EB in mice and the fluorescence intensity and diffusion domain of brain slices were all studied.

RESULTSContrasting to the common microemulsion (ME), HAC-ME at the lower concentration of HAC (<5 mg x mL(-1)) could further improve the transporting of EB across the BBB while EB concentration in other tissues decreased, and Tmax was delayed about 30 min.

CONCLUSIONHAC-ME could facilitate the transporting of EB across the BBB and it was concentration dependent. While the brain targeting absorptive capability of HAC-ME was enhanced.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain ; metabolism ; Chitosan ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Emulsions ; Evans Blue ; chemistry ; pharmacokinetics ; Female ; Hyaluronic Acid ; chemistry ; pharmacokinetics ; pharmacology ; Male ; Mice ; Particle Size ; Tissue Distribution