Imatinib,a small-molecule kinase inhibitor,has proven useful in the treatment of recurrent or metastatic gastrointestinal stromal tumors ,However,resistance to imatinib is a more and more serious problem.This review summarizes the existing knowledge of the imatinib resistance mechanism in gastrointestinal stromal tumors and describes the treatment directions in further.

Adult ; Aged ; Aged, 80 and over ; Biliary Tract Neoplasms ; complications ; Cholangitis ; etiology ; Cholestasis ; etiology ; therapy ; Drainage ; adverse effects ; Female ; Hepatic Encephalopathy ; etiology ; Humans ; Intraoperative Period ; Jaundice, Obstructive ; etiology ; therapy ; Liver Neoplasms ; complications ; Male ; Middle Aged ; Pancreatitis ; etiology ; Stents ; adverse effects

Objective To summary the clinical applied value of interventional therapy in hepatic venous outflow obstruction after orthotopic liver transplantation(OLT).Methods The clinical data of 27 patients suspect with hepatic outflow obstruction out of OLT patients were analyzed retrospec- tively.Most of them presented with liver dysfunction,like ascites,jaundice,or hydropsia of lower ex- tremity as BCS.These patients accepted venography and endovascular treatment if venous outflow ob- struction was found.Results By venography,one case of thrombus in inferior vena cava,one case of hepatic vein stenosis,13 cases of inferior vena cava stenosis(3 cases were associated with hepatic vein stenoses)were identified.Stent implantation was successfully performed on 10 patients,and balloon angioplasty on 4 patients.Rapid,dramatic resolution of symptoms was achieved in those patients. Hepatic vein restenosis occurred in one case 8 months after balloon dilatation,and treated with stent implantation.Inferior vena cava restenosis occurred in one case 2 years after balloon dilation,and trea- ted with another balloon expanding.Patients remained completely asymptomatic at 4 months to 5 years of follow-up.Conclusion The venacavographic balloon angioplasty and metallic stent replacement are safe and useful for post-OLT with venous outflow obstruction.

OBJECTIVETo investigate the effect of Shenqi Fuzheng Injection (SFI) in radiation pneumonitis and its influence on the levels of plasma transforming growth factor beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) at various stages (pre-, mid- and post-radiation) of radiotherapy (RT).

METHODSFifty-eight patients enrolled in this study were randomized into two groups, all received conventional radio therapy, but the treatment group was intravenously dripped with SFI additionally, once daily, starting 3 days before radiotherapy to 1 week after the end of it. Levels of TGF-beta, TNF-alpha and IL-10 in blood samples collected and frozen at different time point of RT, before radiotherapy (Pre-RT), after received 40-50 Gy radiation (Mid-RT) and in time of terminating RT (Post-RT), were measured with enzyme linked immunosorbent assay (ELISA). And the occurrence of radiation pneumonitis was analyzed according to RTOG acute radiation pneumonitis criteria.

RESULTSLevel of TGF-beta increased in both groups after RT, either Mid- or Post-RT, but in comparing with that at Pre-RT, statistical significant (P < 0.05) only showed in the control group at Post-RT time when it raised to peak, while in inter-group comparing insignificance was shown. Level of TNF-alpha also increased in both groups, but statistical significance only showed in the control groups as compared with that of Pre-RT, accordingly, it was lower in the treatment group than that in the control group at corresponding time points (P < 0.05). Level of IL-10 decreased gradually in the process of RT, as compared with that at Pre-RT, significant difference was shown in both groups at Post-RT but not at Mid-RT, as compared between groups, no significance (P < 0.05) was shown, though the treatment group showed a high tendency. As for the ratio of IL-10/TNF-alpha, significant difference of lowering in the control group after RT was shown as compared with that at Pre-RT (P < 0.05), and also as compared with that in the treatment group at corresponding time point (P < 0.05). The occurrence of radiation pneumonia > or = grade 2 in the treatment group was significantly lower than that in the control group (chi2 = 8.7133, P < 0.01).

CONCLUSIONPlasma level of TNF-alpha and ratio of IL-10/ TNF-a could be the practicable indexes for estimating the susceptibility of acute radiation pneumonia; SFI can regulate the network of cytokine, and thus be effective in preventing and treating radiation pneumonitis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; radiotherapy ; Carcinoma, Squamous Cell ; radiotherapy ; Cytokines ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Esophageal Neoplasms ; radiotherapy ; Female ; Humans ; Interleukin-10 ; blood ; Lung Neoplasms ; radiotherapy ; Male ; Middle Aged ; Phytotherapy ; Radiation Pneumonitis ; blood ; prevention & control ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

The aim of this study is to develop a convenient and effective method for the identification of heparin from pigs (include Sus scrofa domestica Brisson and Sus scrofa riukiuanus). Based on sequences of D-loop region of pigs and the other animals, two pairs of highly specific primers were designed for distinguishing heparin of pigs from other animals. The primers were employed to amplify D-loop region of DNA templates extracted from pig and seven other animal species that amounted to 49 samples. AS-PCR (allele-specific PCR) and ARMS (amplification refractory mutation system) were all suitable for fast identification of heparin from pig with anneal temperature at 54-56 degrees C in AS-PCR and with wider anneal temperature in ARMS,at 52-58 degrees C. An about 170 bp DNA fragments were amplified from separately pigs and whereas no DNA fragment was amplified from other samples under the same reaction condition.
Alleles ; Animals ; Base Sequence ; DNA Mutational Analysis ; methods ; DNA Primers ; DNA, Mitochondrial ; genetics ; Drug Contamination ; prevention & control ; Heparin ; analysis ; genetics ; Horses ; genetics ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; methods ; Quality Control ; Ruminants ; genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sus scrofa ; genetics

Objective:Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus,which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients.Methods:This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients.Pharmacokinetic samples were collected from eight pediatric subjects with nephrotic syndrome from Department of Pediatric Nephrology in Peking University First Hospital between June and August 2011.They followed administration of single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n =2),0.05 mg/kg (n =2) and 0.10 mg/kg (n =4).Blood samples were taken before the dose and 1,2,4,6,8,10,12 and 24 h after drug intake.No other medicines or interacting food or drinks were taken during the study period.Blood concentrations were measured using an enzyme multiplied immunoassay technique.Pharmacokinetic analysis was performed using WinNolin Phoenix software Version 6.0 (Pharsight,Cary,NC,USA).Results:The pharmacokinetic data were best described by a non-compartment model.Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows:the maxi mum drug concentrations (Cm=/D) were (1.7 ± 1.0) μg/L,(3.1 ± 1.9) μg/L,(8.0 ± 3.5) μg/L,respectively;Areas under the drug concentration-time curve (AUCo-∞/D) were (47.2 ± 47.1) h · μg/ L,(84.0 ± 13.1) h · μg/L,(175.6 ± 107.1) h · μg/L,respectively;Oral clearance rates were (0.8±0.9) L/(h·kg),(0.4±0.1) L/(h · kg),(1.9 ±1.3) L/(h · kg),respectively;Body weight normalized distribution volumes were (7.0 ± 3.4) L/kg,(12.4 ± 8.4) L/kg and (73.6 ± 68.6) L/kg,respectively.Both mean Cmax normalized level for the administered dose (Cmax/D) and mean AUC0-∞ normalized level for the administered dose (AUC0-∞/D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and 0.10 mg/kg dosage group.There were two peaks in the drug concentrations in every dose group;a primary peak appeared at the end of about 2 h followed by a small secondary peak at h 12,which was more noticeable in the 0.10 mg/kg dose group than in the two lower dosages.Conclusion:The pharmacokinetic characteristics of tacrolimus PR formulation were initially explored in pediatric patients with nephritic syndrome.The data presented form a basis for subsequent larger scale studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome children.

Adult ; Heroin Dependence ; drug therapy ; prevention & control ; Humans ; Male ; Methadone ; therapeutic use ; Patient Compliance ; Treatment Outcome

OBJECTIVETo investigate the dynamic changes of plasma levels of prostacycline (PGI2) and thromboxane A2 (TXA2) and their relationship with the severity of hepatic injury in rats with nonalcoholic fatty liver disease (NAFLD).

METHODSWe established a NAFLD model, with a fat-rich diet consisting of 10% lard oil + 2% cholesterol, which was given to Sprague-Dawley rats (n=48) for a period of 8, 12, 16 and 24 weeks. The other rats were fed standard diets and were used as normal controls (n=24). At sacrifice, liver pathology scores were evaluated and plasma levels of PGI2, its stable metabolic product 6-keto-PGF1 alpha and TXA2, and TXB2 were determined by radioimmunoassay.

RESULTSSimple fatty livers were observed in the model group at 8 weeks. From 12 weeks to 24 weeks, the livers gradually progressed from simple steatohepatitis to liver fibrosis. Plasma levels of TXB2 in the model group increased higher than in the control group after 8 weeks [(52.4+/-3.15) ng/L vs (41.1+/-1.45) ng/L] and continued to increase over time, with the highest levels at 24 weeks [(117.7+/-7.47) ng/L]. A strong positive correlation (r=0.537) was seen between plasma TXB2 levels and the severity of liver injury. Plasma 6-keto-PGF1 alpha concentrations decreased in the model group in comparison with the control group after 8 weeks [(31.1+/-1.62) ng/L vs (36.5+/-1.68) ng/L] and continued to decrease over time, with the lowest concentrations at 24 weeks [(3.4+/-2.43) ng/L t=3.77]. A negative correlation was shown between the 6-keto-PGF1 alpha level and the severity of the liver injury.

CONCLUSIONA rat model of NAFLD was established successfully by feeding a fat-rich diet for 24 weeks. In this model, the imbalance of plasma PGI2 and TXA2 levels (increased TXB2 and decreased 6-keto-PGF1 alpha levels) may play a role in the pathogenesis of experimental NAFLD.

6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Epoprostenol ; blood ; Fatty Liver ; blood ; Liver ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; blood ; Thromboxane B2 ; blood

OBJECTIVETo evaluate the expression of transforming growth factor beta-1(TGF-beta1) and the effects of early drugs intervention of chronic obstructive pulmonary disease(COPD) in rat model.

METHODSThe COPD rat model (group B) was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Drug intervention groups received dongchongxiacao orally daily from the three days before the experiment (group C) and erythromycin by intraperitoneal injection since the third week (group D)and inhalation of budesonide since the forth week (group E). At the end of 10 weeks, all 40 rats including normal control (group A) were assessed for lung resistance (RL) and dynamic lung compliance (Cdyn). The expression of TGF-beta1 gene and protein were also observed by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively.

RESULTSThe changes of pathology and pathophysiology in rat COPD model were similar to those of human COPD. There was a significant increase in the smooth muscle and collagen thickness in the airway wall of the group B in comparison with that of the group A. RL in group B was significantly higher than that in group A (P<0.01), while it was inhibited by early drugs intervention (P<0.01). Cdyn was decreased in group B as compared with that in group A, which was limited by erythromycin and budesonide intervention (P<0.01). The relative content for TGF-beta1 was significantly increased in the epithelial cells of the bronchi, endothelial cells of the pulmonary small vessel and alveolar macrophages of COPD group as compared with those of normal controls (P<0.01).The relative contents for TGF-beta1 in the epithelial of bronchi in group D and group E were significantly lower than that in group B, but not found in group C. There was no difference between group D and group E. There were statistical positive relationships between the RL and the relative content for TGF-beta1 in the bronchial epithelial cells, between the RL and the mRNA level of TGF-beta1 in the lung tissue (P<0.01 approximately 0.05).

CONCLUSIONThis rat COPD model could be helpful to obtain more information about airway remodeling. TGF-beta1 may play an important role during the process of airway remodeling, and could be influenced by early drugs intervention such as budesonide and erythromycin, which may imply their potency in the treatment of COPD. But there is not same phenomenon found in dongchongxiacao group.

Animals ; Anti-Bacterial Agents ; pharmacology ; Anti-Inflammatory Agents ; pharmacology ; Budesonide ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Erythromycin ; pharmacology ; Male ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Transforming Growth Factor beta1

OBJECTIVESepsis remains a serious clinical problem because of high morbidity and mortality. The importance of Toll-like receptors (TLRs) for the induction of immune responses against sepsis was demonstrated in humans. The present study aimed to probe the gene polymorphisms of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg753Gln) in patients with sepsis among Chinese Han children in Wenzhou, and investigate the correlation with sepsis.

METHODThis study was conducted as a case-control study. Using polymerase chain reaction and DNA sequencing, gene polymorphisms of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg753Gln) in 59 children with sepsis, 38 children with severe sepsis (including 20 septic shock) and 57 healthy controls were analyzed. Hardy-Weinberg method of statistics was used to compare the frequency of genotypes alleles among three groups.

RESULTThe mutant genotypes of TLR4 gene (Asp299Gly and Thr399Ile) were not found among sepsis, septic shock and control groups. In severe sepsis group, the Arg753Gln TLR2 polymorphism occurred in 2 out of 38 severe sepsis patients and both of the subjects with the TLR2 Arg753Gln polymorphism had fatal staphylococcal infections.

CONCLUSIONTLR4 gene (Asp299Gly and Thr399Ile) polymorphisms may not be correlated with susceptibility to sepsis among Chinese Han children in Wenzhou. The fact that only 2 out of 38 severe sepsis patients had Arg753Gln TLR2 polymorphism suggests that a larger sample size is needed because of the rarity of the TLR2 allele among Chinese Han children in Wenzhou.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Polymorphism, Single Nucleotide ; Sepsis ; ethnology ; genetics ; Toll-Like Receptor 2 ; genetics ; Toll-Like Receptor 4 ; genetics