Objective To study the reversal effecy of small interfering RNA(siRNA) on multidrug resistance and chemotherpy sensitivity of xenografts human breast cancer tumor,and chemotherpy sensitivity in nude mice.Methods siRNA targeted on multidrug resistance protein(MRP) was transfected into MCF-7 cell xenografts tumors of mice,then the expression level of the MRPmRNA and protein was determined,and the chemotherapeutic sensitivity of the breast cancer tissues was evaluated.Results The RT-PCR and immunohistochemistry results showed that the level of MRPmRNA and protein decreased in the experimental group 24 h after the siRNA was transfected(P

Asialoglycoprotein receptor (ASGPR) is highly expressed on the surface of parenchymal liver cells. It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues, and endocytosed by clathrin-mediated endocytosis, transported and then degraded in lysosome. Based on this character, ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution, reduce potential side effects and lower dose. This article reviewed the expression, structure, ligand binding and endocytosis of ASGPR, and summarized the design and optimization of ASGPR ligands and the release strategies. Finally, we put forward some expects about the clinical drug development for ASGPR.

Objective To develop and test a high precision medical device which allows measurement of bioimpedance in regions below skin surface,and to enable the assessment of strained muscle's situation and instruct patient's rehabilitation exercise.Methods The system was based on the four-electrode impedance measurement mode and designed by using impedance converter network analyzer AD5933 and monolithic operational amplifier AD844.The hardware consisted of an excitation current source,a response signal adjustment circuit,a digital demodulation circuit and a shield driving circuit.This hardware circuit was combined with a LCD screen and a keyboard,which turned it into a portable precision bioimpedance testing device.Results Using an model of three components as test target,a comparison between the device and the Agilent 4294A precision impedance analyzer was presented.In the range of 1 kHz to 100 kHz,the device showed the similar relative error of the complex impedance's modulus and 1 degree absolute error of the complex impedance's phase.The strained muscle's bioelectrical impedance changes in a clinical case during the convalescent were presented and discussed with the results proven to be clinical meaningful.Conclusions The device is accurate,simple and convenient,which is proved qualified on helping doctors to assess the injury states of the strained muscle and to instruct patient's rehabilitation exercise.

Objective: To explore the clinical efficacy of ear acupuncture plus injection at Zusanli (ST 36) in treating shoulder pain after laparoscopic gynecological surgery, and to observe its effect on cytokines. Methods: Two hundred patients with shoulder pain after laparoscopic gynecological surgery were randomized into two groups based on their visiting sequence, 100 cases each. The observation group was intervened by ear acupuncture plus injection at Zusanli (ST 36), and the control group was intervened by oral administration of Ibuprofen, 10 d as a treatment course. The clinical efficacies of the two groups were compared after 2 treatment courses; the visual analogue scale (VAS), present pain intensity (PPI) and 36-item short-form health survey (SF-36) were measured before and after the treatment;the changes of interleukin (IL)-6 and IL-10 after the treatment were also observed. Results: The VAS and PPI scores were significantly changed after the treatment in both groups (both P<0.01). After the treatment, the VAS score in the observation group was significantly different from that in the control group (P<0.05). The component scores of SF-36 were significantly changed after the treatment in both groups (P<0.01); after the treatment, the scores of physical functioning (PF), bodily pain (BP), social functioning (SF), and mental health (MH) in the observation group were significantly different from those in the control group (all P<0.05). The contents of IL-6 and IL-10 dropped significantly after the intervention in both groups (both P<0.01), and the between-group differences were also statistically significant (both P<0.01). The total effective rate of the observation group was higher than that of the control group (P<0.05). Conclusion: Ear acupuncture plus injection at Zusanli (ST 36) can significantly improve the shoulder pain after laparoscopic gynecological surgery, down-regulate the expressions of IL-6 and IL-10, and boost the recovery.

CD4 Antigens ; blood ; CD4-CD8 Ratio ; CD8 Antigens ; blood ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Seizures, Febrile ; immunology

OBJECTIVEConducting the gene characterization of the E6 and E7 gene of human papillomavirus 16 (HPV16) isolated from 15 cases of cervical cancer at Beijing.

METHODSOverlapping primers were designed according to the full-length genomes of E6 and E7 from the GenBank and PCR was used to amplify the E6 and E7 fragments. TA clone was used to select a purified clone in order to have better and valuable sequencing results. Nucleotide and amino acid sequence were analyzed by the Sequencer, Bioedit, Mega et al.

RESULTS8 of 15 (8/15) cervical samples contained HPV E6 and E7 gene, and 4 had Asian type like and 4 had Europe prototype like. There were two nucleotide mutation at E6 position 178 (T-->G,D25E) and at E7 position 647 (A-->G, N29S) in 4 Asian type like viruses. There were one nucleotide mutation at E6 position 335 (C-->T, H78Y) in 1 of 4 Europe prototype like virus. In the cervical cancer samples, 8 of 15 contained the HPV16E 6 and E7 gene. HPV16 E6 and E7 can not be detected in denosquamous carcinoma and adenocarcinoma.

CONCLUSIONHPV16 is the main etiology of the cervical carcinoma. The HPV16 infectious ratio of squamous carcinoma is more than the ratio of adenocarcinoma. 178th nucleotide in E6 gene is the very important site to distinguish the Asia and the Europe prototype strain like. 178 nucleotide in E6 and 647 nucleotide in E7 are the frequent mutation site in cervical carcinoma. Analysis based on the E6 and E7 gene sequence of HPV 16 isolates suggests that naturally occurring sequence variants of E6 and E7 gene may have identify the oncogenic properties.

Adenocarcinoma ; virology ; Carcinoma, Squamous Cell ; virology ; China ; Female ; Human papillomavirus 16 ; chemistry ; genetics ; isolation & purification ; Humans ; Mutation ; Oncogene Proteins, Viral ; chemistry ; genetics ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; virology ; Repressor Proteins ; chemistry ; genetics ; Sequence Homology, Amino Acid ; Uterine Cervical Neoplasms ; virology

Purpose: To evaluate the use of signal intensity index (SII) of skull-base invasion in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI), select a best cut-off SII value to predict the outcome of NPC. Materials and Methods: One hundred and twenty-two NPC patients (92 men, 30 women) with skull-base invasion were included. All patients underwent MRI, signal intensities on T1-weighted imaging (T1WI) were measured for each invaded site and its contralateral normal counterpart. The SIIs were calculated, receiver operating characteristic curves were constructed. The optimal cut-off values were extracted. The overall survival (OS) rates of 5-year follow-up were performed. Results: Sensitivities for differentiating skull-base invasion from normal contralateral anatomy were 98.9%, 88.5% and 70.0%, and specificities were 98.9%, 96.0% and 74.4%, respectively. There were three cut-off values for differentiating invasion from normal anatomy of skull-base, 49%, 98%, and 60%. Significant difference in OS rates (84.2% vs. 57.1%, p=0.007) was seen for SII threshold values > 60% and those ≤ 60%. Conclusions: The SII might be a useful means of differentiating invasion from normal tissue at the skull-base in NPC. The cut-off value of quantitative SII at the skull-base may aid in monitoring the response to treatment of NPC patients.

Aim To investigate the effects of chronic corticos-terone injection on anxiety and depression-like behavior of tree shrews, evaluate the predictability of drug and establish a novel animal model of anxious depression .Methods Twelve Chinese and Burma tree shrews were randomly divided into normal group, model group and venlafaxine group .The anxious depres-sion model of tree shrew was established by chronic corticoster-one injection ( ih, 27 mg· kg-1 , 21 d) .The venlafaxine group received intragastric administration (6 mg· kg-1).Autonomous activity score, sugar water preference test and Morris water maze test were used to evaluate the anxiety and depression-like behav-ior of tree shrews .The expressions of CRH , ACTH and COR in the tree shrew plasma were determined by Elisa kit .The con-tents of monoamine neurotransmitters of tree shrews in the hippo-campus , amygdala and prefrontal cortex were detected by HPLC-ECD.Results Compared with the normal group , the autono-mous activity score , sugar water partial eclipse degree and the learning and memory ability significantly decreased (P<0.01), while the contents of CRH , ACTH and COR significantly in-creased ( P<0.05) , and the contents of 5-HT, NE and DA in the hippocampus , amygdala and prefrontal cortex declined in the model group(P<0.05).In the venlafaxine group, the learning and memory abilities of the tree shrews were improved , the lev-els of CRH and COR in plasma were significantly decreased ( P<0.05), and the contents of 5-HT, NE and DA were increased (P<0.05).Conclusions The tree shrews of anxious depres-sion have obvious HPA axis hyperactivity and monoamine neuro-transmitter disorder , and venlafaxine can reverse this phenome-non, indicating that the tree shrews model of anxious depression has drug predictability , which is a kind of novel animal model of anxious depression closer to human in clinic .

OBJECTIVETo investigate the effect of early intervention by pravastatin with two different dosage on inflammatory factors and endothelial vasodilator function in patients with unstable angina (UA).

METHODS108 patients with UA were investigated consecutively and divided randomly into three groups (group 20 mg, n = 37; group 10 mg, n = 37; group control, n = 34). Blood samples were examined at admission and 4, 8 weeks after the therapy of pravastatin. Fourty patients of UA were chosen from those three groups (15, 15 and 10 cases respectively). The endothelium-dependent vasodilation and the function of vascular endothelium of them were measured. In the dosage of 20 mg pravastatin group non-endothelium-dependent vasodilation in brachial artery was also tested by ultrasound before and 8 weeks after the therapy. Cardiac events were followed up for 2 months.

RESULTS(1) The use of pravastatin in early admission period of UA could significantly reduce inflammatory factors and improve vascular endothelium function, which was more obviously in the group of 20 mg/d than in group of 10 mg/d. These benefits occurred in 4th week and more obviously in 8th week after the therapy. (2) The lipid lowering therapy in the early stage of admission (24 - 48 h) resulted in the reduction of cardiac events in the hospital.

CONCLUSIONThe use of pravastatin 20 mg/d seems better than that of 10 mg/d in all the fields as above in early admission period of UA patients.

Adult ; Aged ; Angina, Unstable ; drug therapy ; Anticholesteremic Agents ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Inpatients ; Male ; Middle Aged ; Pravastatin ; administration & dosage ; therapeutic use ; Prospective Studies

OBJECTIVETo study the effect of embelin on proliferation, differentiation and apoptosis of HL-60 cells and explore its possible mechanism.

METHODSDifferent concentration of embelin were used to treat HL-60 cells. Cell growth curve was analysed by MTT assay, cell apoptosis by Annexin V/PI double staining and JC-1 dye. The differentiation of HL-60 cells was evaluated by expression of CD33, CD34, CD11b and CD14. Bone marrow cells (BMC) from nine patients with acute nonlymphocytic leukemia (ANML) were also studied.

RESULTSEmbelin induced differentiation of HL-60 cells with significant increase of CD14 and CD11b expression at 33.97µmol/L for 3 days (P < 0.01). Embelin induced apoptosis of HL-60 cells in a time- and dose-dependent manner, the apoptosis rates were (9.23 ± 0.05)%, (25.86 ± 0.30)% and (39.03 ± 0.07)% respectively at 339.67 µmol/L of embelin for 12-, 24- and 48-hours treatment (P < 0.05); the apoptosis rates were (0.07 ± 0.03)%, (7.43 ± 0.30)%, (14.01 ± 0.01)%, (25.52 ± 0.03)% and (39.15 ± 0.01)% respectively at 10.19, 33.97, 101.90, 339.67 and 1019.02 µmol/L of embelin for 24-hours culture (P < 0.05). Clusters of differentiation antigen on BMC from three acute promyelocytic leukemia patients showed significant changes at 33.97 µmol/L of embelin treatment for 3 days. Embelin induced apoptosis of BMCs from all the nine ANML patients at 33.97 µmol/L for 24 hour.

CONCLUSIONEmbelin can inhibit proliferation and induce differentiation and apoptosis of HL-60 cells. The mechanism may be related to mitochondrial apoptosis pathway. Embelin at subtoxic concentration doesn't promote leukemia BMC differentiation, but at 339.67 µmol/L induces apoptosis of these cells.

Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism