Objective To explore the clinical efficacy and side effect of hepatocyte growth - promoting factor in treatment of infant hepatitis syndrome. Methods Sixty one cases of infant hepatitis syndrome were chased as the treatment group who hospitalized in our hospital from March 2002 to Feb 2003,and 54 cases of infant hepatitis syndrome as control group who hospitalized during March 2001 to Feb 2002. The treatment group were administrated with hepatocyte growth - promoting factor for 2 weeks. We obser-ved the recovery of patient's liver function (TBIL.ALT, AST) and the side effect of hepatocyte growth- promoting factor after two weeks of the treatment. Results After the treatment,TBIL and ALT decreased significantly in the treatment group of infant hepatitis syndrome. The treatment group was superior to the control group (P

Background:Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options,ultimately leading to right heart failure and death.Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH.However,the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated.This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism.Methods:PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT).3-BrPA,or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up,and indices such as right ventricular systolic pressure (RVSP),right ventricular hypertrophy index (RVHI),pulmonary arteriolar remodeling indicated by percent media thickness (％ MT),lactate levels and glucose consumption,were evaluated.Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections.Western blotting,immunohistochemistry,and/or immunofluorescence analyses were used to measure the expression of relevant proteins.A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis.Results:MCT-induced PH showed a significant increase in glucose consumption (0 vs.4 weeks:0.87 ± 0.23 vs.2.94 ± 0.47,P =0.0042) and lactate production (0 vs.4 weeks:4.19 ± 0.34 vs.8.06 ± 0.67,P =0.0004).Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ± 0.35 vs.3.25 ± 0.47,P =0.0063),lactate production (5.09 ± 0.55 vs.8.06 ± 0.67,P =0.0065),MCT-induced increase in RVSP (39.70 ± 2.94 vs.58.85 ± 2.32,P =0.0004),pulmonary vascular remodeling (％ MT,43.45％±1.41％ vs.63.66％±1.78％,P＜0.0001),and right ventricular hypertrophy (RVHI,38.57％ ± 2.69％ vs.62.61％ ± 1.57％,P ＜ 0.0001) when compared with those of the PBS-treated group.3-BrPA,a hexokinase 2 inhibitor,exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1,inducing apoptosis,and suppressing inflammation.Conclusions:3-BrPA might have a potential beneficial effect on the PH treatment.

AIMTo observe the differences of hemodynamics and nitric oxide synthase(NOS) activity of ventricular cardiac muscle in two septic shock models and explore the possible mechanism.

METHODSTwo rat models of septic shock[lipopolysaccharide(LPS)-induced and cecal ligation and puncture (CLP)-induced septic shock] were used. The hemodynamic parameters and nitric oxide synthase activity of ventricular cardiac muscle were measured.

RESULTSThe hemodynamic parameters in CLP-induced model were increased in the early stage and decreased in the late stage while in LPS-induced model the parameters showed the same change of the CLP late stage. Both LPS model and CLP model (late stage) showed significant increase in NOS activity, but there was no difference between the two models. After treatment of the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), the parameters of CLP-late stage and LPS model increased significantly. The NOS activity reached the highest level in the CLP-middle stage. The production of nitrite/nitrate decreased significantly in LPS model and CLP model(late stage) after treatment of L-NAME, but the nitrite/nitrate produced by constitutive NOS in LPS model was higher than CLP model(late stage).

CONCLUSIONThe increase of the NOS activity may be the main reason to lead to the depression of the hemodynamic parameters. Inducible NOS may play the leading role in the LPS model while cNOS and iNOS have the same effect in the CLP model.

Animals ; Hemodynamics ; Lipopolysaccharides ; Male ; Myocytes, Cardiac ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; classification ; metabolism

Adolescent ; Bacteria ; isolation & purification ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Respiratory Tract Infections ; microbiology

Objective To analyze the relation between ~(99)Tc~m-DTPA renal dynamic imaging and pathological changes in patients with lupus nephritis (LN).Methods Ten normal control and 29 patients with LN underwent ~(99)Tc~m-DTPA renal dynamic imaging.The LN patients were divided into two groups:silent LN (SLN) group,18 patients;and obvious LN (OLN) group,11 patients.For each case,glomerular filtration rate (GFR),peak time (t_p),half excretion time (t_(1/2)) and the excretion rate at 20 min (R_(20)) were calculated.Assessment of renal function on the scintigraphic images was evaluated by nuclear medicine physicians.The t-test,Fisher'exact probability and R×C association were used for data analysis.Results There were significant differences between normal people and two goups of LN in tp(t=5.3,9.3,both P＜0.05),t_(1/2)(t=6.9,12.0,both P＜0.05)and R_(20)(t=10.1,12.1,both P＜0.05).As to GFR,there was significant decrease in OLN patients(t=4.1,P＜0.05),but not in SLN patients(t=1.7,P＞0.05).Diagnoses of renal function by renal dynamic imaging were compared with the renal pathological changes (r=0.2273,P＜0.05).Conclusions ~(99)Tc~m-DTPA renal dynamic imaging is useful for evaluation of the early stage renal function for LN patients and to diagnose LN patients with no symptom of renal impairment.It may help to assess the degree of renal parenchymal damage while obviating the need for renal biopsy in these patients.

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

OBJECTIVETo find the best condition of the preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex.

METHODL9(3(4)) table was used to examine the effects of 4 factors, and the inclusion rate of each test was determined of orthogonal test.

RESULTThe best condition was:oil:beta-cyclodextrin:water = 1:8:60 (mL:g:mL), stirring for 1 hour at 80 degrees C.

CONCLUSIONThe complex prepared on the condition aforementioned is stable and stirring has a highest inclusion rate.

Cyclodextrins ; Drug Carriers ; Drug Stability ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; Flowers ; chemistry ; Magnolia ; chemistry ; Oils, Volatile ; administration & dosage ; isolation & purification ; Plants, Medicinal ; chemistry ; Technology, Pharmaceutical ; methods ; beta-Cyclodextrins

Adolescent ; Adult ; Aged ; Ankle Joint ; pathology ; physiopathology ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Tuberculosis, Osteoarticular ; drug therapy ; pathology ; physiopathology ; surgery ; Young Adult

OBJECTIVETo investigate the vascular effect of acute and chronic treatment of interferon-alpha (IFN-alpha) in rat aortic rings.

METHODSIsolated thoracic aortic rings were mounted on the organ bath and the tension of the vessel was recorded.

RESULTSIFN-alpha(10, 100, 1,000 and 10,000 U/ml) caused concentration -dependent relaxation of endothelium-intact aorta rings preconstricted with phenylephrine (PE,10(-6)mol/L), to(90.1+/-0.91)%, (65.1+/-5.21)%, (39.5+/-8.22)% and (35.3+/-8.27)% of pre-drug control, respectively. Removal of the endothelium inhibited the relaxation by IFN-alpha. The vasorelaxant effect of IFN-alpha (100 U/ml ) was attenuated by pretreatment with L-NAME (10(-4)mol/L), methylene blue (10(-5)mol/L) or AMG (10(-4)mol/L), to (97.2+/-5.34)%, (95.1+/-6.25)% and (93.7+/-8.82)% of the control, respectively. Pretreatment with IFN-alpha (1,000,000 U/d, i.p.) for five days markedly inhibited the endothelium-dependent relaxation of the aortic rings to acetylcholine. But the endothelium-dependent relaxation to acetylcholine was not changed by pretreatment of IFN-alpha (10,000 U/ml) with the isolated aorta rings for 2 h.

CONCLUSIONThe vasorelaxation induced by IFN-alpha in rat aorta rings is endothelium-dependent and is possibly mediated by inducible nitric oxide synthase. Chronic treatment of IFN-alpha may impair the endothelium or NO-sGC pathway.

Acetylcholine ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Endothelium, Vascular ; physiology ; Guanylate Cyclase ; physiology ; Interferon-alpha ; pharmacology ; Male ; Nitric Oxide ; physiology ; Nitric Oxide Synthase ; physiology ; Nitric Oxide Synthase Type II ; Phenylephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects

AIMTo study the metabolic kinetics of MN9202 in Beagle dog liver microsome.

METHODSBeagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.

RESULTSThe Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.

CONCLUSIONIt was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Calcium Channel Blockers ; metabolism ; pharmacokinetics ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP3A Inhibitors ; Dihydropyridines ; metabolism ; pharmacokinetics ; Dogs ; Ketoconazole ; pharmacology ; Microsomes, Liver ; metabolism ; Mixed Function Oxygenases ; antagonists & inhibitors ; Nitrobenzenes ; metabolism ; pharmacokinetics ; Tranylcypromine ; pharmacology ; Troleandomycin ; pharmacology