Objective To explore the liver toxicities of the VDLD scheme in children with malignant tumor.Methods In a prospective trial,the levels of serum total protein,albumin, globulin,rate of albumin/globuin alanine aminotransferase,aspartate transaminase,gamma glutamyltranspeptidase,total bile acid and alkaline phosphatase were tested in children with malignant tumour before and after VDLD scheme,and compared with each other.Results The concentration of the serum total bile acid was significantly increased after VDLD scheme than before(P

AIMTo establish the fundamentals for the design of scutellarin prodrug and formulation with feasible physicochemical and biopharmaceutical properties by esterifying scutellarin, an active component with poor absorption extracted from Erigeron breviscapus of Chinese medicine.

METHODSWith the method of salifying followed by esterifying, ethyl and benzyl ester of scutellarin were synthesized. Glycolamide ester of scutellarin was also synthesized with an improved method. Their structures were confirmed by MS and 1H NMR. The solubility and partition coefficient of the prodrugs were determined and their degradations were investigated in various buffers and in human plasma. The emulsion and cyclodextrin complex of glycolamide ester were prepared and the protection of the ester from degradation was compared in the intestinal tract contents. Furthermore, the degradation of glycolamide ester in the homogenates of various intestinal segments was studied. Results Three prodrugs were synthesized successfully and their structures were confirmed. Glycolamide ester of scutellarin showed better stability in the aqueous solution (t(1/2) approximately =16 d, pH 4.2) and the shortest half-life in the human serum (t(1/2) approximately =7 min). Compared with scutellarin, the solubility of glycolamide ester was increased about ten times in pH 4.0 buffer, and about thirty five times in water. Partition coefficient of the glycolamide ester increased significantly from -2.56 to 1.48. However, the ester degradation in the homogenates of intestinal mucus would be an obstacle for its absorption. The degradation rates were in the order duodenum > ileum > or = jejunum > colon. The emulsion showed a better protection of glycolamide ester from the degradation than cyclodextrin complex.

CONCLUSIONGlycolamide ester of scutellarin shows better physicochemical properties than ethyl and benzyl eater of scutellarin, but its stability in intestinal tract needs to be improved. The emulsion or / and colon-targeted delivery may be selected as one of strategies to decrease the presystemic degradation.

Animals ; Apigenin ; chemistry ; isolation & purification ; pharmacokinetics ; Emulsions ; Erigeron ; chemistry ; Esters ; Flavones ; chemical synthesis ; chemistry ; pharmacokinetics ; Glucuronates ; chemistry ; isolation & purification ; pharmacokinetics ; Glucuronides ; chemical synthesis ; chemistry ; pharmacokinetics ; Humans ; Intestinal Mucosa ; metabolism ; Intestines ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Prodrugs ; chemical synthesis ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Malignant tumor is one of the main causes for death in the world at present as well as a major disease seriously harming human health and life and restricting the social and economic development. There are many kinds of reports about traditional Chinese medicine patent prescriptions, empirical prescriptions and self-made prescriptions treating cancer, and prescription rules were often analyzed based on medication frequency. Such methods were applicable for discovering dominant experience but hard to have an innovative discovery and knowledge. In this paper, based on the traditional Chinese medicine inheritance assistance system, the software integration of mutual information improvement method, complex system entropy clustering and unsupervised entropy-level clustering data mining methods was adopted to analyze the rules of traditional Chinese medicine prescriptions for cancer. Totally 114 prescriptions were selected, the frequency of herbs in prescription was determined, and 85 core combinations and 13 new prescriptions were indentified. The traditional Chinese medicine inheritance assistance system, as a valuable traditional Chinese medicine research-supporting tool, can be used to record, manage, inquire and analyze prescription data.
Drug Prescriptions ; Humans ; Medicine, Chinese Traditional ; Neoplasms ; drug therapy

AIMTo establish RP-HPLC method for determination of plasma scutellarin concentration and study of the pharmacokinetic behavior of scutellarin in rat after ig administration of breviscapine and its beta-cyclodextrin complex (breviscapine-beta-CD).

METHODSMobile phase composed of methanol and acetate buffer. The column was Shim-pack C18. Twelve rats randomized into 2 groups were separately given breviscapine and breviscapine-beta-CD at single dose of 10.8 mg.kg(-1). Drug in plasma was extracted and determined by HPLC. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSLinearity was obtained over the range of 10-400 ng.mL(-1). The recovery was 95.32%-98.81%. C(max) and AUC(0-12 h) of breviscapine were (154 +/- 18) ng.mL(-1) and (710 +/- 126) ng.h.mL(-1). For breviscapine-beta-CD, C(max) and AUC(0-12 h) were (328 +/- 31) ng.mL(-1) and (1,093 +/- 200) ng.h.mL(-1), respectively. There were significant differences of AUC(0-12 h) between breviscapine and breviscapine-beta-CD (P < 0.01).

CONCLUSIONThe assay method was suitable for the determination of scutellarin plasma concentration in rat. Brevescapine-beta-CD showed greater absorption compared with that of brevescapine.

Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Drug Compounding ; Erigeron ; chemistry ; Flavonoids ; blood ; isolation & purification ; pharmacokinetics ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; beta-Cyclodextrins ; blood ; pharmacokinetics

Objective To investigate the clinical significance of external obturation with cotton ball in treatment of digestive tract lip shape fistula. Methods A prospevtive randomixed controllde study was conducted in 30 patients with digestive tract lip shape fistula admitted from January 2001 to November 2007,which were divided into experimental group ( 15 patienets) and control griup ( 15 patjients). The control group received traditional fistula mouth continuous drainage,with fastomg or part enteral nutrition and parenteral nutrition. The experimernal group received external obturatiion with cotton ball,with controling spills of oineteatinal fluid and resuming normal eating and activetes, The patients general information, fistuala mouth sixe, volume, weight, albumin, determinstic operation time, postoperative complications, hospital, signficantly reduced fistula, flow, postoperative compared between the two groups. Results Compared with the control group , significantly redced fistula, flow, postoperative complivations and cost, increased wdighe and albumin,as well as shortened operation time and hospital stay were found oin the experimetal grou. Conclusin External obturation with cotton ball is safe effective methde in treatment of digestive tract lip shape fistula, obviusly shortening the course of disease, redcing patients'cost and pain, and rapidly improving patients nutritional status.

Objective To report a case of deep mycosis caused by Rhizomucor chlamydosporus. Methods Medical history,histopathology and laboratory examination were investigated,and fungal identifi- cation by microscopy and culture as well in the patient.Results The patient,a 41-year-old male,initially presented with mild-tender and progressively aggravating masses on the right glutea,both groins,and back of the head of pancreas.Later,ulcer,necrosis,and black crusts developed at the primary lesions accompanied with nausea,vomitting and dysfunction of liver.Pathological examination revealed a chronic granuloma- tous inflammation in the dermis and subcutaneous tissue;and branching,nonseptate and broad hyphae in multinuclear giant cells,tissue spaces and blood vessel lumens,and,few PAS-positive septate hyphae as well as basophilic chlamydospores located in multinuclear giant cells.The isolate was identified as R. chlamydosporus.Conclusions The case of deep mycosis caused by R.chlamydosporus began with invasive granuloma,followed by necrotic ulcer,with condition aggravating rapidly,and the patient finally died of se- rious cachexia.

OBJECTIVETo study the mechanism of gene JWA involved in oxidative stress under hydrogen peroxide (H(2)O(2)) exposure.

METHODSBoth MCF-7 (human breast cancer cell line) and WI-38 (human embryo lung fibroblast cell line) cells were treated with 1 mmol/L of H(2)O(2) with or without pre-incubation of taurine (tau). Malondialdehyde (MDA) and glutathione (GSH) contents in supernatant of cell culture were measured; RT-PCR and Western blotting were carried out for evaluation of the expressions of JWA mRNA and protein respectively. Heat shock proteins (HSP27, HSP70 and HSP90) were also analyzed.

RESULTSThe contents of MDA before and after H(2)O(2) treatment in MCF-7 cells were (0.531 +/- 0.038), (0.674 +/- 0.410) mmol/L respectively, (P < 0.01), while those in WI-38 cells were (0.572 +/- 0.035), (0.683 +/- 0.028) mmol/L respectively, (P < 0.01). The contents of GSH before and after H(2)O(2) treatment in MCF-7 cells were (0.053 +/- 0.002), (0.044 +/- 0.002) g/L respectively, (P < 0.01), while those in WI-38 cells were (0.058 +/- 0.002), (0.050 +/- 0.002) g/L respectively, (P < 0.01). The expression of JWA mRNA was down regulated, at 6 h it decreased by 68.4%, while in WI-38 cells no obvious change found. JWA protein and HSP27 showed markedly increased after H(2)O(2) treatment in both cells but not in similar extent.

CONCLUSIONOxidative stress signal pathways of JWA gene varied between cancer and non-cancer cell lines; JWA protein may have a similar function as HSP27 and act as an important signal molecule in H(2)O(2) induced cell injury.

Blotting, Northern ; Cell Line ; Cell Line, Tumor ; Gene Expression Regulation ; drug effects ; Glutathione ; metabolism ; HSP70 Heat-Shock Proteins ; metabolism ; HSP90 Heat-Shock Proteins ; metabolism ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Hydrogen Peroxide ; administration & dosage ; Intracellular Signaling Peptides and Proteins ; Malondialdehyde ; metabolism ; Oxidative Stress ; RNA, Messenger ; drug effects ; genetics ; metabolism

To explore the effect of a tyrosine-kinase inhibitor STI571 and P21(WAF) gene clone on the proliferation, cycle, apoptosis of leukemia cell line K562, P21(WAF) gene was obtained by RT-PCR, and its sequence was approved to be correct, then P21-pcDNA3.1 vector was constructed and transfected into K562 cell line. After selected with G418, P21-pcDNA3.1-K562 cell clone that stably expression P21(WAF) was isolated. P21(WAF) protein was identified by Western blot. The survival rate were tested by MTT. Cell cycle and apoptosis were tested by flow cytometry. The results showed that the expression of P21(WAF) protein could be detected by Western blot in P21-pcDNa3.1-K562 cells. A strong inhibition of cell proliferation was observed in P21-pcDNA3.1-K562 cells as compared with that of the control. The cells cycle were arrested in G(0)/G(1) phase. The percentage of apoptosis was declined slightly after P21-pcDNA3.1-K562 cells were combined with STI571, meanwhile its survival rate declined more slowly than that of K562 cell with STI571. In conclusion, P21(WAF) inhibits the proliferation of K562 cell, meanwhile slightly inhibits its apoptosis induced by STI571and decrease its sensitivity to STI571.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Base Sequence ; Benzamides ; Blotting, Western ; Cell Cycle ; drug effects ; genetics ; Cell Proliferation ; drug effects ; Cloning, Molecular ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; pathology ; Molecular Sequence Data ; Piperazines ; pharmacology ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; Transfection

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

Objective To study the feasibility and clinical values of diffusion tensor tractography (DTT)in the spinal cord at 3.0 T MR.Methods Forty patients with spinal cord compression including cervical cord herniation and cervical spondylosis(30 cases),tumors in spinal canal(9 cases)and old injury in cervical vertebrae(1 cases)and 20 healthy volunteers participated in this study.Single-shot spin- echo echo-planar diffusion tensor sequence for tractography of the spinal cord was performed.The fibers of spinal cord were visualized by using fiber tracking software.Results On the DTT maps,the normal spinal cord was depicted as a fiber tract showing color-encoded cephaloeaudally,which indicated anisotropy in the cephalocaudal direction.By setting two ROI,the main spinal cord fiber tracts,such as corticospinal or spinothalamic tract,were visualized.The tracts from two sides of the brain did not completely cross.It was asymmetric in the number of tracts on the two sides in most normal subjects(8/10).The tracts of all patients with cord compression were seen oppressed or damaged in different degrees.The DrrT in patients with cervical spondylosis and extramedullary-intradural neurolemmoma demonstrated that tracts were oppressed but not damaged.The DTT in one ependymoma showed that tract was markedly compressed and slightly damaged.Conclusion DTT is a promising tool for demonstrating the spinal cord tracts and abnormalities,can provide useful information for the localization of compression and evaluation of the impairment extent on the white matter tracts of the spinal cord.