Clinical study of modified Ganmai Dazao decoction in the treatment of yang deficiency climacteric depression and observe the effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with yang deficiency climacteric depression. 86 cases were randomly divided into treatment group treated with modified Ganmai Dazao decoction and control group treated with Deanxit. The curative effect was evaluated with Hamilton's depressive scale (HAMD) and pittsburgh sleep quality scale (PSQI) before and at the end of the two and four weeks of the treatment, the serum levels of serotonin (5-HT), norepinephrine (NE), estradiol (E2), follicle stimulating hormone (FSH), luteotropic hormone (LH) were detected before and after the four weeks of the treatment The results showed that the total effective power of treatment group was 88.4% and the total effective power of control group was 81.4% after four weeks interference, with insignificant difference between the two groups. After two and four weeks of the treatment, the score of HAMD decreased remarkably in both groups (P < 0.01), with insignificant difference between the two groups in same phase. After two and four weeks of the treatment, the total score of PSQI decreased remarkably in both groups (P < 0.05), with significant difference between the two groups after four weeks (P < 0.01). After four weeks of treatment, the serum levels of 5-HT and NE increased (P < 0.01), with insignificant difference between the groups. After four weeks of treatment, the serum levels of E2 increased obviously (P < 0.05), the levels of FSH decreased obviously (P < 0.05), the levels of LH decreased insignificant, with insignificant difference between two groups. This study indicates that modified Ganmai Dazao decoction has obvious therapeutic effects in the treatment of climacteric depression, and showed equivalent efficacy with Deanxit, and modified Ganmai Dazao decoction has better effect on improving the sleep quality in patients than Deanxit, the effect of improved clinical symptoms may be through adjusted levels of 5-HT, NE, E2, FSH and LH of climacteric depression.
Adult ; Depression ; blood ; drug therapy ; etiology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Menopause ; drug effects ; psychology ; Middle Aged ; Neurosecretory Systems ; drug effects ; metabolism ; Norepinephrine ; blood ; Phytotherapy ; Serotonin ; blood

To silence the expression of K-RASAsn12 in human pancreatic cancer cell line by vector-based RNAi(RNA interference) technique,two single-strand DNA sequences encoding mutant-specific shRNA (short haipin RNA) for K-RASAsn12 were synthesized and then inserted into pSilenCircle. The recombinant plasmid was called pSC-K-RASAsn12. According to the same method, pSC-GFP encoding shRNA for GFP was gained. Both recombinant plasmids were transfected into human pacreatic cancer cell line AsPC-1 and BxPC-3. The expression level of K-RASAsn12 was detected by semi-quantitative RT-PCR and Western blot. The result indicated that the recombinant plasmid edcoding mutant-specific shRNA for K-RASAsn12 can inhibit significantly the expression of K-RASAsn12 without affection of wild-type K-RAS(K-RASWT)in Human Pancreatic Cancer Cell Line.

Cycloartane triterpenoids, which exist widely in nature, are mainly distributed in Astragalus (Leguminosae) species, Trib. Cimicifuga (Ranunculaceae) and Thalictrium (Ranunculaceae) species and possess various bioactivities. Along with the development of isolation techniques of phytochemistry, more and more this kind of compounds are isolated and identified. However, bioactivity researches on the compounds are relatively lagged behind. Most researches are still in screening level, deficient in mechanism elucidation, short of action proven in vivo and SAR analysis. The author summarized the bioactivity of this kind of compounds from all aspects: anti-tumor, anti-virus, antibacterial, anti-inflammation, immune-regulatory, cardiovascular system, hepatic protection and so forth. This will be benefit for the further research and development of the compounds.
Animals ; Anti-Infective Agents ; isolation & purification ; pharmacology ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Astragalus Plant ; chemistry ; Cimicifuga ; chemistry ; Humans ; Plants, Medicinal ; chemistry ; Thalictrum ; chemistry ; Triterpenes ; isolation & purification ; pharmacology

Objective To evaluate the effect of cytochrome P450 2 D6*10 ( CYP2 D6*10 ) polymorphism on the pharmacokinetics of oral nebivolol after single and multiple doses. Methods Fifteen healthy volunteers which were selected according to their CYP2D6*10 genotype, consisted of 8 of CYP2D6*1 carriers and 7 of CYP2D6*10/*10 geno-types.All subjects received a single dose of 5 mg and multiple doses (5 mg? d-1 , qd, for 7 days) .Nebivolol in plasma were measured by LC-MS/MS.The main pharmacokinetic parameters were calculated by WinNonlin program.Results The main pharmacokinetic parameters of nebivolol in plasma between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes after a single dose were as follows: t1/2 were (9.88 ±5.47), ( 12.29 ±6.19 ) h, AUCinf were ( 7.26 ±5.88 ), (8.56 ±5.20)μg? L-1? h, Cmax were (1.11 ±0.53), (1.42 ±0.75)μg? L-1 , respectively.The main pharmacokinetic parameters of nebivolol in plasma between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes after multiple doses were as follows:t1/2 were (8.56 ±2.38), (7.67 ±4.75) h, AUCinf were (10.62 ±5.62), (12.74 ±7.40)μg? L-1? h, Cmax were (2.05 ±0.83), (2.02 ±0.75)μg? L-1, respectively.No significant differences in the pharmacokinetic parameters of nebivolol were found between CYP2D6*1 carriers and CYP2D6*10/*10 genotypes.The clearance of the multiple doses was significantly lower compared with that of single dose in the different genotyped groups.Conclusion CYP2D6*10 polymorphism has no significant effect on the pharmacokinetics of oral nebivolol after single and multiple doses.The elimination of nebivolol decreases after the multiple doses, which is not affected by CYP2D6*10 polymorphism.

Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from the 2009 H1N1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the United States, indicating that H3N2 SwIV might be a potential threat to public health. Since southern China is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the possibility of SwIV infection at agricultural fairs. In this study, a high-growth reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and tested as a candidate inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed, with significantly reduced lung lesion and viral loads in vaccine-inoculated mice relative to mock-vaccinated controls. These results suggest that the GD/PR8 vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV outbreaks in China.
Animals ; Female ; Influenza A Virus, H3N2 Subtype/*genetics/immunology ; Influenza Vaccines/genetics/immunology/*therapeutic use ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/immunology/*prevention & control/virology ; Reassortant Viruses/genetics/immunology ; Reverse Genetics/methods/*veterinary ; Swine ; Swine Diseases/immunology/*prevention & control/virology ; Vaccines, Inactivated ; Virus Replication

A terminal deoxynucleotidyl transferase ( TdT ) amplification based DNA-copper nanoclusters (CuNCs) sensor was developed for detection of L-histidine ( L-His). Single strand DNA containing poly-thymine ( T) sequences were synthesized by TdT in the presence of dTTP. In blank control, poly-T sequences worked as templates of CuNCs due to the affinity between thymine and copper ions( II) . Fluorescence intensity was enhanced when CuNCs formed with reducing agents. In the presence of L-His, the imidazolyl group of L-His worked as a chelating agent that formed L-His-Cu2+ chelated complex. Thus less copper ions were induced in poly-T sequences, and less CuNCs were obtained to produce week fluorescence signals. A good linear correlation was obtained between fluorescence change and the logarithm of the L-His concentration over the range of 5. 0 ×10-9-5. 0 ×10-4 mol/L. The detection limit was estimated as 3. 4 ×10-9 mol/L. And the recoveries were 97. 4%-104. 6% for the actual urine samples. Compared with other methods of synthetic CuNCs, this method allowed to specifically determining L-histidine without template or labeling, which showed good potential in biomedical and clinical analysis.

OBJECTIVETo explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient.

METHODSThe FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR.

RESULTSFVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months.

CONCLUSIONThis is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.

Autoantibodies ; immunology ; Factor VIII ; genetics ; Hemophilia A ; genetics ; Humans ; Immune Tolerance ; drug effects ; Immunosuppression

OBJECTIVETo investigate the feasibility and risk of preimplantation genetic diagnosis (PGD) for screening normal offspring of Robertsonian translocation carriers.

METHODSThis case was clinically diagnosed as primary infertility for 6 years; the husband was found to have chromosome der (13;14) (q10;q10) and oligozoospermia. For the solution of the couple's problem, controlled ovarian hyperstimulation (COH) and intracytoplasmic sperm injection (ICSI) were performed to obtain embryos. The embryos were drilled in zona by acidified Tyrode's solution at 6-8 cell stage (day 3 post-fertilization) and a single blastomere was removed from each embryo. All blastomeres were analyzed by fluorescence in situ hybridization (FISH) using the double color probes LSI 13q labeled by SpectrumOrange and Tel 14q labeled by SpectrumGreen. The embryos biopsied were cultured at once and the normal ones selected were transferred the next day. Prenatal diagnostic techniques were used to detect the karyotype of fetus at 18 weeks of gestation.

RESULTSUnbalanced, normal or balanced, and unclear embryos were separated. The couple obtained 50a (4/8)normal or balanced,and 37.5a (3/8)unbalanced, and 12.5a (1/8) unclear embryos. A singleton pregnancy followed, and the karyotype of the fetus (46,XY) was detected by prenatal diagnostic techniques.

CONCLUSIONPGD is useful for screening out unbalanced embryos and is very valuable for solving the reproductive problem of Robertsonian translocation carriers and for avoiding fetal beings with severe disorders.

Adult ; Blastocyst ; cytology ; metabolism ; Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Embryo Implantation ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Infant, Newborn ; Male ; Pregnancy ; Preimplantation Diagnosis ; methods ; Sperm Injections, Intracytoplasmic ; Translocation, Genetic ; genetics

Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.
Animals ; Antibodies, Viral/blood ; Antigens, Viral/genetics/*immunology ; Body Weight ; Cross Protection/*immunology ; Disease Models, Animal ; Epitopes, T-Lymphocyte/genetics/immunology ; Female ; Influenza A Virus, H3N2 Subtype/genetics/*immunology ; Influenza Vaccines/*immunology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/*immunology/mortality/pathology/prevention & control ; Peptides/genetics/*immunology ; Random Allocation ; Survival Analysis ; Vaccines, Synthetic/immunology ; Virus Replication

This study was aimed to investigate the effects of low frequency and power ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell line K562/A02 in vitro, to find out the parameters of optimal exposure, and to explore the possible mechanism reversing drug-resistance of K562/A02 cells. The K562/A02 cells in logarithmic growth phase were used in experiments. The experiments were divided into 4 groups: group control, group adriamycin (A02) alone, group ultrasound (US) alone and group A02+US. The trypan blue dye exclusion test and MTT assay were used to determine the cell viability; Wright's staining was used to detect the apoptosis; the flow cytometry was used to analyze the drug concentration, and the scanning electron microscopy was used to observe the changes of cell surface. The results showed that the significant differences in cell viability, intracellular adriamycin concentration and changes of cell membrane were found between ultrasound-treated and untreated cells in the presence of various concentration of adriamycin. The exposure to ultrasound at 20 kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60 seconds could kill K562/A02 cells at once. After being treated by low frequency ultrasound, the small holes with diameter about 1-2 microm in the cell surface appeared. The ultrasound increased the adriamycin concentration in the cells, accelerated the formation of apoptotic bodies, and promoted apoptosis of adriamycin-resistant cells. It is concluded that the ultrasound at optimal parameters enhances inhibitory effect of adriamycin on drug-resistant cell line, thereby reverses drug-resistance of drug-resistant cell line through sound-hole effect in tumor cells resulting from ultrasound induced cavitation.
Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; K562 Cells ; Ultrasonics