Objective: To investigate the relationship of chemokine receptor with the development and progression of primary biliary cirrhosis (PBC). Methods: Real-time PCR and flow cytometry were used to examine the mRNA and protein expression of chemokine receptor 1 (CCR1), CCR3 and CCR5 in the peripheral blood mononuclear cells (PBMCs) of 60 patients with PBC, 60 patients with hepatitis B-related cirrhosis, and 60 normal controls. Total bilirubin (TBIL) and γ-glutamyltransferase (γ-GT) levels were determined in the patients with PBC and normal controls,and their correlation with chemotactic factors was also analyzed. Results: Both the mRNA and protein expression levels of CCR1, CCR3 and CCR5 in the PBMCs were significantly lower in PBC patients than those in the other two groups (P< 0.05), and there were no significant differences between the latter two groups. The mRNA and protein levels of CCR1, CCR3 and CCR5 were significantly lower in patients with stage III and IV PBC than those with stage I and II PBC. CCR1 protein expression was correlated with TBIL levels in PBC patients(r= - 0.445,P<0.01), but not with γ-GT(r= - 0.230,P>0.05). CCR3 protein was not linearly correlated with TBIL level (r= -0.173,P>0.05),but was correlated with γ-GT(r= -0.295, P< 0.05). Expression of CCR5 protein was negatively correlated with both TBIL and γ-GT levels(r= -0.531,P<0.01; r=-0.665,P <0.01). Conclusion: CCR1, CCR3 and CCR5 expression is associated with the development and progression of PBC; they may be involved in the regulatory mechanism of PBC,which may cast new lights on the diagnosis and prevention of PBC.

Objective To explore the effect of nitric oxide (NO) on ?-aminobutyric acid B receptor (GABA_BR) subunits during recurrent febrile seizures (FS).Methods Twenty-four Sprague-Dawley rats aged 21 days were randomly divided into 4 groups: control group (37.0 ℃ water,n=8), FS group (45.2 ℃ water,n=8), FS + SNP group (45.2 ℃ water,n=8), FS+L-NMMA group (45.2 ℃ water,n=8). FS rats were induced 10 times in a warm-water bath, once every 2 days. The plasma level of NO was detected by the spectrophotometer. The expressions of GABA_BR subunit mRNA and c-fos gene were examined by in situ hybridization. The expressions of GABA_BR subunit and Fos protein were observed by immunohistochemistry. Results The plasma level of NO increased in FS + SNP group while decreased in FS+L-NMMA group compared with that in FS group. The expressions of GABA_BR_2 were down-regulated in FS+SNP group, while GABA_BR_1 hardly changed compared with those in FS group. In FS+L-NMMA group, both the expression of GABA_BR_2 and GABA_BR_1 up regulated compared with those in FS group. The expressions of c-fos gene and Fos protein were significantly enhanced after recurrent FS. SNP elevated the expressions of c-fos gene and Fos protein, while L-NMMA down regulated the expressions of them.Conclusion NO may play a regulatory role through modulating GABA_BR function in the pathogenesis of recurrent FS.

Objective To explore the influence of ?-aminobutyric acid B receptor(GABA_BR)on carbon monoxide (CO)/heme oxygenase(HO-1)system during recurrent febrile seizures (FS).Methods Sprague-Dawley rats aged 21 days were randomly divi- ded into 4 groups:control group and FS group,FS+baclofen group,FS+phaclofen group.FS in rats were induced 10 times in a bath of warm water, once every 2 days.The plasma level of CO was detected by the dual wave lengh spectrophotometer;the expressions of GABA_BR and HO-1 mRNA were examined by insitu hybridization;the expressions of GABA_BR and HO-1 protein were observed by immunohistochemistry.Results The plasma level of CO increased in FS+baclofen group,while decreased in FS+phaclofen group compared with FS group.The expressions of GABA_BR and HO-1 upregulated in FS+baclofen group,while decreased in FS+phaclofen group compared with FS group.There were significant difference (All P

The study aims to characterize and compare interferon reference standards from 5 manufacturers. By testing molecular mass and trypsin-digested peptide mass mapping, the amino acid sequence was verified and post-translational modifications such as disulfide bond were identified. Results show that the molecular mass and amino acid sequence were consistent with theory; the disulfide bonds of 4 lots of interferon were Cys1-Cys98/Cys29-Cys138, 1 lot was Cys29-Cys139/Cys86-Cys99; N-terminal "+Met", acetyl N-terminal and Met oxidation were identified in part of the sample. UPLC-MS can be used to characterize and compare interferon reference standards from different manufacturers.
Amino Acid Sequence ; Chromatography, High Pressure Liquid ; methods ; Interferons ; standards ; Mass Spectrometry ; methods ; Molecular Weight ; Oxidation-Reduction ; Peptide Mapping ; Protein Processing, Post-Translational ; Reference Standards

One new dicyclopeptide cyclo-(L-N-methyl Glu-L-N-methyl Glu) (1), together with one new natural dicyclopeptide cyclo-(L-methyl Glu ester-L-methyl Glu ester) (2), and two known dicyclopeptides cyclo-(L-methyl Glu ester-L-Glu) (3), and cyclo-(L-Glu-L-Glu) (4), were isolated from the aerial parts of Dianthus chinensis L. Their structures were determined by spectroscopic analyses and chemical methods.
Dianthus ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry

To investigate the effects and potential mechanisms of hyperoside (Hyp) on the vascular endothelium function in middle cerebral artery (MCA) ex vivo in rats. Isolated arterial segments from MCAs of rats were used for surveying vasomotoricity in a pressurized chamber. Transmembrane potential was recorded by using glass microelectrodes to evaluate hyperpolarization. Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) was utilized to observe the effect on 1 x 10(-7) mol . L-1 U46619-preconstricted MCA in rats. The results showed that 1 x 10(-6)-1 x 10(-4) mol . L-1 Hyp significantly induced concentration-dependent vasodilatation and hyperpolarization, leading to the maximal diastolic ratio of (73. 2 ± 6. 1)% and maximal changes in membrane potentials of (-13. 2 ± 2. 2) mV. Hyp still elicited vasorelaxation and hyperpolarization by removal of endothelium in MCA of rat, which was notably attenuated as compared with vascular endothelium-intact group (P <0. 01). In the MCAs preconstricted by U46619 (1 x 10(-7) mol . L-1), Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) produced concentration-dependent vasorelaxation and hyperpolarizition that were partially attenuated by 3 x 10(-5) mol . L-1 L-NAME(a NOS inhibitor) plus 1 x 10(-5) mol . L-1 PGI2 ,(a synthetase inhibitor). The residual effects were further decreased by 1 x 10(-3) mol . L-1 TEA (an inhibitor of Ca2+-activated potassium channel) or 1 x 10(-5) mol . L-1 PPG (a blocker of endogenous H2S synthese-CSE). Similarly, 1 x 10(-5)-1 x 10(-3) mol . L-1 NaHS (a donor of exogenous H2S) or 1 x 10(-5)-1 x 10(-3) mol . L-1 L-Cys (the substrate of endogenous H2S synthesis) obviously evoked dose-dependent vasodilatation and hyperpolarization of MCA in rats. These findings indicated that Hyp may induce endothelium-dependent and endothelium-independent responses. And the endothelium-dependent vasodilatation may be related to the increases of endogenous H2S that has been promoted Hyp in the endotheliocyte of MCAs, and activated Kca and opening of Kca channels, resulting in the hyperpolarization of vascular smooth muscle cell membrane and subsequent reduction of Ca2+ influx and vasodilation.
Animals ; Endothelium, Vascular ; drug effects ; Enzyme Inhibitors ; pharmacology ; Female ; Male ; Middle Cerebral Artery ; Muscle, Smooth, Vascular ; drug effects ; Nitric Oxide ; metabolism ; Potassium Channels ; metabolism ; Quercetin ; analogs & derivatives ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfides ; metabolism ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

OBJECTIVETo evaluate the efficacy of late accelerated hyperfractionated conformal radiotherapy (LACF) combined with capecitabine on esophageal carcinoma.

METHODSOne hundred and sixty eight patients of esophageal cancer were randomly divided into 3 groups, including the radiotherapy alone group (CF) which received conventional conformal radiotherapy to a total of 60 - 66 Gy, LCAF group which received conventional fractionated conformal radiotherapy during the first two-thirds of the treatment to a dose about 40 Gy/20F/4W, then followed by late accelerated hyperfractionated conformal radiotherapy, twice daily radiotherapy at 1.3 Gy per fraction to a total dose about 64 - 69 Gy, and LCAF + C group (late accelerated hyperfractionated radiotherapy combined with capecitabine), in which patients were treated as the same as the LCAF group, except that they were treated with capecitabine (1.5 g po bid) from beginning of the radiotherapy to the end.

RESULTSThe short-term results of the 3 groups were 74.0%, 85.5% and 95.2%, respectively (P = 0.006). The local control rates at 1, 3 and 5 years were 64.0%, 30.0%, 24.0% in the CF group, 81.8%, 65.5%, 58.2% in the LCAF group and 90.1%, 77.8%, 74.6% in the LCAF+C group, respectively. The 1-, 3- and 5-year survival rates of the 3 groups were 58.0%, 20.0%, 8.0%; 78.2%, 36.4%, 17.0% and 85.7%, 55.6%, 30.2%, respectively. The effect of LCAF+C group was better than that of LCAF group and CF group. The incidence of acute tracheitis and acute esophagitis in the LCAF+C group and LCAF group was higher than that in the CF group, but there was no stastistically significant difference between the 2 groups. There was no statistically significant difference in distant metastasis in the 3 groups.

CONCLUSIONSCapecitabine, as an effective chemosensitizater combined with late accelerate hyperfractionated radiotherapy can improve the short-term results of treatment of esophageal cancer. The value of this combined treatment in distant metastasis reqires further study in the clinic.

Antimetabolites, Antineoplastic ; therapeutic use ; Capecitabine ; Carcinoma, Squamous Cell ; mortality ; pathology ; therapy ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Dose Fractionation ; Esophageal Neoplasms ; mortality ; pathology ; therapy ; Esophagitis ; etiology ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; adverse effects ; methods ; Remission Induction ; Survival Rate

The stable and controllable quality of decoction pieces is an important factor to ensure the efficacy of clinical medicine. Considering the dilemma that the existing standardization of processing mode cannot effectively eliminate the variability of quality raw ingredients, and ensure the stability between different batches, we first propose a new strategy for Chinese medicine processing technologies that coupled with individuation processed and cybernetics. In order to explain this thinking, an individual study case about different grades aconite is provided. We hope this strategy could better serve for clinical medicine, and promote the inheritance and innovation of Chinese medicine processing skills and theories.
Chemistry, Pharmaceutical ; methods ; standards ; Cybernetics ; standards ; Drug Therapy ; standards ; Drugs, Chinese Herbal ; chemistry ; standards ; toxicity ; Humans ; Quality Control

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.
Animals ; Creatine Kinase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Ischemic Preconditioning, Myocardial ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; prevention & control ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Quercetin ; administration & dosage ; analogs & derivatives ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

Autopsy ; Female ; Hepatoblastoma ; diagnosis ; diagnostic imaging ; pathology ; Humans ; Infant, Newborn ; Liver Neoplasms ; diagnosis ; diagnostic imaging ; pathology ; Neoplasm Staging ; Rare Diseases ; Tomography, X-Ray Computed