OBJECTIVETo study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) combined Erlotnib on the growth of A549 xenograft in nude mice and its mechanism.

METHODSThe xenograft model in nude mice was established by inoculating A549 cells subcutaneously. BALB/c nude mice bearing A549 xenograft were randomly divided into six groups, i.e., the low dose Erlotinib group (A) , the standard dose Erlotnib group (B) , the low dose Erlotinib combined AETC group (C), the standard dose Erlotnib combined AETC group (D), the AETC group (E), the control group (F), 12 in each group. Different medication was performed for 7 successive weeks after 24 h. One mL blood was withdrawn and tumor tissues taken. The tumor inhibition rate was calculated. The combined effect was analyzed by Jin's Formula [Q = Ea + b/(Ea + Eb-Ea x Eb) ]. mRNA and protein expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), and B cell lymphoma-2 (Bcl-2) in xenografts were detected using real-time RT-PCR and ELISA.

RESULTSCompared with Group F, the xenograft weight was obviously lowered in Group B-E (P < 0.05, P < 0.01). The q value was 0.92 in Group C and 0.96 in Group D, which was obtained by simple adding of the two drugs. Compared with Group F, EG- FR mRNA expression in Group D and E, COX-2 mRNA expression in Group A-E; Bcl-2 mRNA expression in Group B-D; COX-2 protein expression in Group B-E; Bcl-2 protein expression in Group C and D were obviously lowered with statistical difference (P < 0.05, P < 0.01).

CONCLUSIONSAETC combined low dose and standard dose Erlotinib had synergistic effect on tumor inhibition. Its mechanism might be associated with down-regulating mRNA and protein expression levels of COX-2 and Bcl-2.

Animals ; Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Erlotinib Hydrochloride ; pharmacology ; Heterografts ; Lung Neoplasms ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptor, Epidermal Growth Factor ; metabolism ; Taxus ; Transplantation, Heterologous

Adolescent ; Adult ; Arsenic Poisoning ; drug therapy ; Child ; Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy

Objective To investigate the changing pattern of antimicrobial resistance among gram-negative bacilli isolated from respiratory intensive care unit (RICU) for rational use of antimicrobial agents.Methods Antimicrobial susceptibility of 1 047 isolates of gram-negative bacilli from 2000 to 2004 was tested by disk diffusion method.WHONET 5.3 software was used to analyze the data.Results The most common pathogens were Pseudomonas aeruginosa (42.9%),Stenotrophomonas malto- philia (17.1%),Acinetobacter baurnannii (10.0%) and Klebsiella pneumoniae (6.5%).The susceptibility rate of P.aerug- inosa was relatively higher to ceftazidime (50%-74%),amikacin (33.3%-81.0%),piperacillin-tazobactam (30.4%-64.6%) and cefoperazone-sulbactam (33.5%-47.5%),while the susceptibility to imipenem decreased.The susceptibility rate of S. maltophilia was relatively higher to cefoperazone-sulbactam (47.2%-78.6%) and ticarcillin-clavulanic acid(28.3%-86.6%). More than 90% of Acinetobacter baumannii isolates were susceptible to imipenem.The susceptibility rates of K.pneumoniae to imipenem and cefepime were 92.9%-100% and 55.6%-80.0%,respectively.The susceptibility rate to piperacillin-tazobac- tam decreased from 58.3% to 21.7%.The prevalence of extended-spectrum?-lactamases (ESBLs) in K.pneumoniae increased from 11.1% in 2002 to 47.8% in 2004.Conclusions Most pathogens show significant resistance to the most commonly used an- tibiotics.It is very important to select antibiotics for the treatment of infections in ICU based on the results of susceptibility.

Background and purpose:Chemotherapy plays an important role in the treatment of breast carcinoma by inhibiting the tumor growth and inducing the apoptosis.MAPK transduction pathway is closely related to proliferation and apoptosis of varieties of tumor cells,inhibition of MAPK pathway may increase the efficiency and decrease the toxicity of chemotherapy.Our study was to investigate the effect of MEK inhibitor PD98059 in response of breast cancer cell lines to Epirubicin.Methods:Human breast cancer cell lines MCF-7 and MCF-7/ADR were used as cell models.Epirubicin(EADM),PD98059(inhibitor of MAPK Kinase-MEK),or EADM+PD98059 was added into the culture medium,the expression of MEK2 and p-ERK were measured by Western blot,the growth of the two cell lines were measured by MTT.Results:ERK activity was elevated in MCF-7 after the treatment of EADM,the cells were more sensitive to EADM if combined with PD98059,while in MCF-7/ADR,ERK activity kept unchanged after EADM treatment,and PD98059 has no effect on the sensitivity of cells to EADM.Conclusion:MAPK signal transduction may be activated in some cells treated by EADM,adding inhibitor of MAPK signal transduction could improve the sensitivity of the cells to EADM.

OBJECTIVETo observe the effect and the possible mechanism of Jiexiao Oral Liquid (JXOL) in preventing and curing virus induced asthma in children.

METHODSOne hundred and sixty patients of acute upper respiratory tract infection (AURTI) with asthma history were randomly divided into 2 groups. JXOL was given to the treated group within 24 hrs after occurrence of AURTI symptoms, and virazole of 10-15 mg.kg-1.d-1 was given to the control group, the therapeutic course for both groups was 7 days. Changes of clinical symptoms, signs, therapeutic effect, pulmonary function and immuno-globulin in patients were observed.

RESULTSThe total effective rate of the treated group was 83.8%, the clinical control rate was 48.8%, while those in the control group were 62.5% and 23.8% respectively, showing significant difference between them (P < 0.01). JXOL could obviously improve the indexes of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), reduce the level of IgE, as compared with those before treatment, the difference was significant (P < 0.01 or P < 0.05); it also showed significant difference as compared with those in the control group after treatment. The changes of IgA, IgG and IgM after treatment showed insignificant difference.

CONCLUSIONJXOL was effective in preventing and curing virus induced asthma in children, it also shows pulmonary function improving and immune regulating effects.

Adolescent ; Asthma ; drug therapy ; prevention & control ; virology ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; Male ; Phytotherapy ; Respiratory Tract Infections ; complications ; virology

Objective: To explore the determinants for health-seeking behavior of the residents after cough for more than 3 weeks in Yiwu, Zhejiang Province, in order to provide reference for prevention and control of respiratory diseases. Methods: A multi-stage cluster random sampling method was used to recruit the community residents aged 5 years and above in Yiwu. A face-to-face questionnaire survey was conducted to collect demographic information, features of cough and health-seeking behaviors in the past month. The multivariate logistic regression model was employed to analyze the associated factors for health-seeking behavior after a cough for more than 3 weeks. Results: Among 6 374 residents investigated, 152 cases had a cough for more than 3 weeks in the past month, accounting for 2.48%. They were( 45.00±21.15 ) years old, including 70 ( 46.05% ) males and 82 ( 53.95% ) females. About 58.55% ( 89 ) of them sought medical treatment. The results of multivariate logistic regression analysis showed that females ( OR=2.100, 95%CI: 1.005-4.391 ), middle school education level ( OR=0.406, 95%CI: 0.168-0.983 ), family annual income of 100 000 to 199 999 yuan ( OR=2.993, 95%CI: 1.215-7.373 ) were associated factors for health-seeking behavior after a cough for more than 3 weeks. Conclusion The rate of health-seeking behavior after a cough for more than 3 weeks among the residents in Yiwu is 58.55%, which is associated with gender, education level and income.

The aim of this study was to obtain the soluble protein of human pregnane X receptor ligand binding domain (PXRLBD) through the coexpression of PXRLBD and 88 amino acids of steroid receptor coactivator-1 (SRC88) and apply the protein to constructing a new model of screening PXR ligands. Expression plasmid of pETDuet-1-SRC88-PXRLBD was constructed and transformed into Escherichia coli Rosetta (DE3) to coexpress PXRLBD and SRC88 via induction by IPTG at low temperature. Then an equilibrium dialysis model was constructed to study the interaction between PXRLBD and drugs including clotrimazole and dexamethasone, using HPLC as the analysis method. The results showed that the soluble protein of PXRLBD was obtained and the HPLC data indicated that clotrimazole bound to PXRLBD, while dexamethasone did not bind to PXRLBD, which indicated the successful establishment of a new method for studying the interaction between PXR and drugs. The new method may be useful in the screening of PXR ligands in vitro.
Clotrimazole ; metabolism ; Dexamethasone ; metabolism ; Dialysis ; methods ; Drug Interactions ; Escherichia coli ; genetics ; metabolism ; Histone Acetyltransferases ; genetics ; metabolism ; Humans ; Ligands ; Nuclear Receptor Coactivator 1 ; Plasmids ; Protein Binding ; Receptors, Steroid ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Transformation, Genetic

Objective:To conduct a glucagon like peptide-1(GLP-1)controllability model rat by chemical genetics, and observe the impact of GLP-1 neuron excitability on appetite.Methods:Fifteen rats were evenly divided into Green fluorescent protein(GFP)group, HM3D group, and HM4D group. Various combinations of adeno-associated virus(rAAV)were injected into the nucleus tractus solitarius(NTS). rAAV-GLP-1-cre and rAAV-GFP-dio were administered in rats of GFP group. The rats of HM3D group were injected with rAAV-GLP-1-cre and rAAV-HM3D-mCherry-dio while rAAV-GLP-1-cre and rAAV-HM4D-mCherry-dio were injected in rats of HM4D group . The optimal dose of clozapine N-oxide(CNO)was selected based on feeding behavior and body weight changes of rats after intraperitoneal injection of different doses of CNO. The controllability of GLP-1 neurons was confirmed by comparing with intraperitoneal injection of saline. The number of activated GLP-1 neurons in the NTS area and the expression of POMC neurons in the hypothalamus were detected 30 minutes after CNO injection.Results:GLP-1 neurons in the NTS area of rats were successfully labeled. The rat of HM3D group revealed a decrease in food intake( P=0.021)while the rat of HM4D group showed an increase( P=0.002), when given 1 mg/kg of CNO, no changes at the dose of 0.5 mg/kg and 3.0 mg/kg. Immunofluorescence showed that the activity of GLP-1 neurons in NTS of GFP group was lower than that of HM3D group( P=0.022), and higher compared with that of the HM4D group( P=0.049). The expression of GLP-1 neurons in NTS and POMC neurons in the hypothalamus of the HM3D group after intraperitoneal injection of CNO was also higher than that in the HM4D group( P=0.003). Conclusion:Using chemical genetics technology, GLP-1 controllability model rat could be successfully established via injecting varying combinations of rAAV into the NTS area of rat. Injection of 1 mg/kg CNO can effectively activate or inhibit the neuron to regulate appetite.

OBJECTIVETo investigate the diagnosis and surgical treatment of adult Hirschsprung disease (AHD).

METHODSClinical data of 10 patients with AHD undergoing operation from May 1985 to May 2005 were analyzed retrospectively.

RESULTSThere were 7 males and 3 females with an age ranged from 14 to 40 years. All the cases had constipation, and were diagnosed by barium enema. Aganglionosis was located in distal sigmoid and rectum in 2 cases, in rectum in 7 cases, unknown in one case. Colostomy was performed in one, Ikeda s operation in 6, Rehbein operation in two,modified Swenson operation in one. After radical operation,7 patients had excellent continence function, one had good function, one had poor function.

CONCLUSIONSThe diagnosis of adult HD mainly depends on the history of constipation, barium enema and manometry examination. The pull-through procedures are effective surgical treatments for adult HD. The operation type should be selected individually.

Adolescent ; Adult ; Female ; Hirschsprung Disease ; diagnosis ; surgery ; Humans ; Male ; Young Adult

BACKGROUNDTuberculosis (TB) is a chronic wasting inflammatory disease characterized by multisystem involvement, which can cause metabolic derangements in afflicted patients. Metabolic signatures have been exploited in the study of several diseases. However, the serum that is successfully used in TB diagnosis on the basis of metabolic profiling is not by much.

METHODSOrthogonal partial least-squares discriminant analysis was capable of distinguishing TB patients from both healthy subjects and patients with conditions other than TB. Therefore, TB-specific metabolic profiling was established. Clusters of potential biomarkers for differentiating TB active from non-TB diseases were identified using Mann-Whitney U-test. Multiple logistic regression analysis of metabolites was calculated to determine the suitable biomarker group that allows the efficient differentiation of patients with TB active from the control subjects.

RESULTSFrom among 271 participants, 12 metabolites were found to contribute to the distinction between the TB active group and the control groups. These metabolites were mainly involved in the metabolic pathways of the following three biomolecules: Fatty acids, amino acids, and lipids. The receiver operating characteristic curves of 3D, 7D, and 11D-phytanic acid, behenic acid, and threoninyl-γ-glutamate exhibited excellent efficiency with area under the curve (AUC) values of 0.904 (95% confidence interval [CI]: 0863-0.944), 0.93 (95% CI: 0.893-0.966), and 0.964 (95% CI: 00.941-0.988), respectively. The largest and smallest resulting AUCs were 0.964 and 0.720, indicating that these biomarkers may be involved in the disease mechanisms. The combination of lysophosphatidylcholine (18:0), behenic acid, threoninyl-γ-glutamate, and presqualene diphosphate was used to represent the most suitable biomarker group for the differentiation of patients with TB active from the control subjects, with an AUC value of 0.991.

CONCLUSIONThe metabolic analysis results identified new serum biomarkers that can distinguish TB from non-TB diseases. The metabolomics-based analysis provides specific insights into the biology of TB and may offer new avenues for TB diagnosis.

Adult ; Aged ; Biomarkers ; blood ; Chromatography, High Pressure Liquid ; methods ; Female ; Humans ; Male ; Mass Spectrometry ; methods ; Middle Aged ; Tuberculosis ; blood